Cellulose diacetate (CDA) is a biobased plastic with high strength and marine biodegradability; however, its applications are limited by intrinsic brittleness. In this study, a series of block copolymers (BCPs) composed of poly(ε-caprolactone) (PCL; A block) as a soft segment and poly(N-vinylpyrrolidone) (PVP; B block) as a CDA-compatible segment were synthesized as toughening additives for CDA. Incorporation of the PVP segment into the BCPs suppressed macrophase separation of PCL, leading to the formation of dispersed PCL domains with radii of 4.4−19.4 nm. The mechanical properties of the CDA films were improved by adding 10 wt % BCPs, with toughness increasing 4.09- to 12.4-fold over neat-CDA depending on BCP architecture. BAB- and AB2-type BCPs were more effective than AB-type BCPs, correlating with their ability to generate smaller domains and reduce the interdomain spacing (ligament thickness). In particular, significant toughness enhancement was observed when the ligament thickness was reduced to <60 nm.
{"title":"Toughening of Cellulose Diacetate Through Microphase-Controlled Blending of Poly(ε-Caprolactone)−Poly(N-Vinylpyrrolidone) Block Copolymers","authors":"Sho Fukushima, Takaya Kobayashi, Yuki Tsuji, Satoshi Katsuhara, Weeranuch Lang, Feng Li, Takuya Yamamoto, Kenji Takahashi, Kenji Tajima, Toshifumi Satoh, Takuya Isono","doi":"10.1021/acs.biomac.6c01399","DOIUrl":"https://doi.org/10.1021/acs.biomac.6c01399","url":null,"abstract":"<p>Cellulose diacetate (CDA) is a biobased plastic with high strength and marine biodegradability; however, its applications are limited by intrinsic brittleness. In this study, a series of block copolymers (BCPs) composed of poly(ε-caprolactone) (PCL; A block) as a soft segment and poly(<em>N</em>-vinylpyrrolidone) (PVP; B block) as a CDA-compatible segment were synthesized as toughening additives for CDA. Incorporation of the PVP segment into the BCPs suppressed macrophase separation of PCL, leading to the formation of dispersed PCL domains with radii of 4.4−19.4 nm. The mechanical properties of the CDA films were improved by adding 10 wt % BCPs, with toughness increasing 4.09- to 12.4-fold over neat-CDA depending on BCP architecture. BAB- and AB<sub>2</sub>-type BCPs were more effective than AB-type BCPs, correlating with their ability to generate smaller domains and reduce the interdomain spacing (ligament thickness). In particular, significant toughness enhancement was observed when the ligament thickness was reduced to <60 nm.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 10","pages":"6814–6825"},"PeriodicalIF":5.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteoarthritis (OA) is a degenerative joint disease characterized by the failure of cartilage lubrication and persistent inflammation induced by friction-generated debris. Therefore, an effective OA treatment strategy should simultaneously enhance joint long-term lubrication and suppress inflammation. Toward this goal, we developed durable Lipo/PADM microgels via multiple cross-linking to integrate sustained lubrication with matrix metalloproteinase (MMP)-responsive dexamethasone release. The microgels maintained a low coefficient of friction of 0.029, remaining 24.3% lower than PBS after 8 weeks of in vitro degradation. In the MMP-rich OA microenvironment, ester-bond cleavage enabled sustained, on-demand drug release, reaching 70% within 14 days. Lipo/PADM microgels restored type II collagen expression, suppressed MMP-13 in bone marrow mesenchymal stem cells, and alleviated the OA-associated catabolic microenvironment. Intra-articular administration significantly reduced cartilage degeneration and delayed OA progression. These poly(glutamic acid)-based microgels offer a promising OA therapy through durable lubrication, responsive drug delivery, and prolonged intra-articular retention.
Osteoarthritis (OA) is a degenerative joint disease characterized by the failure of cartilage lubrication and persistent inflammation induced by friction-generated debris. Therefore, an effective OA treatment strategy should simultaneously enhance joint long-term lubrication and suppress inflammation. Toward this goal, we developed durable Lipo/PADM microgels via multiple cross-linking to integrate sustained lubrication with matrix metalloproteinase (MMP)-responsive dexamethasone release. The microgels maintained a low coefficient of friction of 0.029, remaining 24.3% lower than PBS after 8 weeks of in vitro degradation. In the MMP-rich OA microenvironment, ester-bond cleavage enabled sustained, on-demand drug release, reaching 70% within 14 days. Lipo/PADM microgels restored type II collagen expression, suppressed MMP-13 in bone marrow mesenchymal stem cells, and alleviated the OA-associated catabolic microenvironment. Intra-articular administration significantly reduced cartilage degeneration and delayed OA progression. These poly(glutamic acid)-based microgels offer a promising OA therapy through durable lubrication, responsive drug delivery, and prolonged intra-articular retention.
{"title":"Poly(l‑glutamic Acid)-Based Microgels with Long-Term Synergistic Lubrication and MMP-Responsive Anti-Inflammatory Delivery for Osteoarthritis Therapy","authors":"Rong Wu, Yanyang Chen, Junyu Wu, Kaixuan Ren, Wenguo Cui, Jingbo Yin","doi":"10.1021/acs.biomac.6c00920","DOIUrl":"10.1021/acs.biomac.6c00920","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by the failure of cartilage lubrication and persistent inflammation induced by friction-generated debris. Therefore, an effective OA treatment strategy should simultaneously enhance joint long-term lubrication and suppress inflammation. Toward this goal, we developed durable Lipo/PADM microgels via multiple cross-linking to integrate sustained lubrication with matrix metalloproteinase (MMP)-responsive dexamethasone release. The microgels maintained a low coefficient of friction of 0.029, remaining 24.3% lower than PBS after 8 weeks of in vitro degradation. In the MMP-rich OA microenvironment, ester-bond cleavage enabled sustained, on-demand drug release, reaching 70% within 14 days. Lipo/PADM microgels restored type II collagen expression, suppressed MMP-13 in bone marrow mesenchymal stem cells, and alleviated the OA-associated catabolic microenvironment. Intra-articular administration significantly reduced cartilage degeneration and delayed OA progression. These poly(glutamic acid)-based microgels offer a promising OA therapy through durable lubrication, responsive drug delivery, and prolonged intra-articular retention.</div></div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by the failure of cartilage lubrication and persistent inflammation induced by friction-generated debris. Therefore, an effective OA treatment strategy should simultaneously enhance joint long-term lubrication and suppress inflammation. Toward this goal, we developed durable Lipo/PADM microgels via multiple cross-linking to integrate sustained lubrication with matrix metalloproteinase (MMP)-responsive dexamethasone release. The microgels maintained a low coefficient of friction of 0.029, remaining 24.3% lower than PBS after 8 weeks of in vitro degradation. In the MMP-rich OA microenvironment, ester-bond cleavage enabled sustained, on-demand drug release, reaching 70% within 14 days. Lipo/PADM microgels restored type II collagen expression, suppressed MMP-13 in bone marrow mesenchymal stem cells, and alleviated the OA-associated catabolic microenvironment. Intra-articular administration significantly reduced cartilage degeneration and delayed OA progression. These poly(glutamic acid)-based microgels offer a promising OA therapy through durable lubrication, responsive drug delivery, and prolonged intra-articular retention.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (153KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (153KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6058-6073"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>A persistent challenge in the development of biobased materials is to balance sustainability with robust mechanical properties and specific functionalities. In this context, the present study provides a structure-guided functionalization strategy that offers a viable route toward this goal by integrating the introduction of functional groups into biobased feedstocks with precise control over polymer architecture. Specifically, a novel fluorinated biobased bisphenol monomer was synthesized. Its high steric bulk and fluorinated nature effectively reduce the material’s dielectric constant and enhance hydrophobicity, thereby broadening the functional application scope of biobased polymers. Furthermore, by designing a terpolymer system incorporating rigid, semirigid, and flexible segments, a substantial increase in toughness was achieved without significantly compromising thermal stability. The resulting material exhibits a tensile strength of 51.5 MPa, an elongation at break of 75%, a low dielectric constant of 2.48 at 1 MHz, and a water contact angle of 90°. This work demonstrates that combining sterically demanding fluorinated monomers with a synergistic rigid-flexible architecture provides an effective pathway for functionalizing biobased materials and toughening high-performance polymers.</div></div><div>A persistent challenge in the development of biobased materials is to balance sustainability with robust mechanical properties and specific functionalities. In this context, the present study provides a structure-guided functionalization strategy that offers a viable route toward this goal by integrating the introduction of functional groups into biobased feedstocks with precise control over polymer architecture. Specifically, a novel fluorinated biobased bisphenol monomer was synthesized. Its high steric bulk and fluorinated nature effectively reduce the material’s dielectric constant and enhance hydrophobicity, thereby broadening the functional application scope of biobased polymers. Furthermore, by designing a terpolymer system incorporating rigid, semirigid, and flexible segments, a substantial increase in toughness was achieved without significantly compromising thermal stability. The resulting material exhibits a tensile strength of 51.5 MPa, an elongation at break of 75%, a low dielectric constant of 2.48 at 1 MHz, and a water contact angle of 90°. This work demonstrates that combining sterically demanding fluorinated monomers with a synergistic rigid-flexible architecture provides an effective pathway for functionalizing biobased materials and toughening high-performance polymers.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (83KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (83KB)</sp
{"title":"Synthesis of Fluoro-Functional Biobased Polycarbonates with Superior Comprehensive Performance for Potential 5G Communication Applications","authors":"Jingnan Xu, Yi Cheng, Mingze Xia, Ziyue Jiao, Jiaming Liang, Zuxin Yao, Zhiyong Wei","doi":"10.1021/acs.biomac.6c01078","DOIUrl":"10.1021/acs.biomac.6c01078","url":null,"abstract":"<div><div>A persistent challenge in the development of biobased materials is to balance sustainability with robust mechanical properties and specific functionalities. In this context, the present study provides a structure-guided functionalization strategy that offers a viable route toward this goal by integrating the introduction of functional groups into biobased feedstocks with precise control over polymer architecture. Specifically, a novel fluorinated biobased bisphenol monomer was synthesized. Its high steric bulk and fluorinated nature effectively reduce the material’s dielectric constant and enhance hydrophobicity, thereby broadening the functional application scope of biobased polymers. Furthermore, by designing a terpolymer system incorporating rigid, semirigid, and flexible segments, a substantial increase in toughness was achieved without significantly compromising thermal stability. The resulting material exhibits a tensile strength of 51.5 MPa, an elongation at break of 75%, a low dielectric constant of 2.48 at 1 MHz, and a water contact angle of 90°. This work demonstrates that combining sterically demanding fluorinated monomers with a synergistic rigid-flexible architecture provides an effective pathway for functionalizing biobased materials and toughening high-performance polymers.</div></div><div>A persistent challenge in the development of biobased materials is to balance sustainability with robust mechanical properties and specific functionalities. In this context, the present study provides a structure-guided functionalization strategy that offers a viable route toward this goal by integrating the introduction of functional groups into biobased feedstocks with precise control over polymer architecture. Specifically, a novel fluorinated biobased bisphenol monomer was synthesized. Its high steric bulk and fluorinated nature effectively reduce the material’s dielectric constant and enhance hydrophobicity, thereby broadening the functional application scope of biobased polymers. Furthermore, by designing a terpolymer system incorporating rigid, semirigid, and flexible segments, a substantial increase in toughness was achieved without significantly compromising thermal stability. The resulting material exhibits a tensile strength of 51.5 MPa, an elongation at break of 75%, a low dielectric constant of 2.48 at 1 MHz, and a water contact angle of 90°. This work demonstrates that combining sterically demanding fluorinated monomers with a synergistic rigid-flexible architecture provides an effective pathway for functionalizing biobased materials and toughening high-performance polymers.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (83KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (83KB)</sp","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6121-6133"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-09-14Epub Date: 2026-08-12DOI: 10.1021/acs.biomac.6c00930
Debasish Nath, Jahanvi Ralhan, Pallavi S. Chaubey, Manisha Nirwan, Asish Pal
<div><div>Neurodegenerative disorders pose a major global health challenge due to impaired electrical signaling in nerve fibers, yet effective regenerative therapies remain limited. Here, we report an injectable hydrogel that integrates intrinsic conductivity, antioxidative capacity, and strain-stiffening mechanics, to emulate key features of the neural extracellular matrix (ECM) and promote neuronal differentiation. We design peptide amphiphiles (<strong>Fc</strong> <sub> <strong>n</strong> </sub>, <em>n</em> = 5, 10) by anchoring a redox-active ferrocene (Fc) motif to a self-assembling peptide segment (<sup> <em>N</em> </sup>VFFAKK<sup> <em>C</em> </sup>) via methylene spacers (<em>n</em>). These nanofibers are dynamically cross-linked with a thermoresponsive polymer, <strong>P</strong> <sub> <strong>DMA</strong> </sub>, via Schiff-base chemistry to furnish <strong>Fc</strong> <sub> <strong>n</strong> </sub>-<strong>P</strong> <sub> <strong>DMA</strong> </sub> hydrogels exhibiting tunable electrical conductivity, potent radical-scavenging ability, and nonlinear strain-stiffening behavior. Notably, the hydrogels display both heat- and strain-induced stiffening behavior reminiscent of fibrin networks. <em>In vitro</em> experiments show that SH-SY5Y neuroblastoma cells encapsulated in these hydrogels, particularly <strong>Fc</strong> <sub> <strong>10</strong> </sub>-<strong>P</strong> <sub> <strong>DMA</strong> </sub>, exhibit excellent biocompatibility, resistance to oxidative stress, and enhanced neurite outgrowth. Taken together, the multifunctional hydrogels provide a biomimetic 3D niche that leverages electrical, mechanical, and redox cues to synergistically promote neurogenesis.</div></div><div>Neurodegenerative disorders pose a major global health challenge due to impaired electrical signaling in nerve fibers, yet effective regenerative therapies remain limited. Here, we report an injectable hydrogel that integrates intrinsic conductivity, antioxidative capacity, and strain-stiffening mechanics, to emulate key features of the neural extracellular matrix (ECM) and promote neuronal differentiation. We design peptide amphiphiles (<strong>Fc</strong> <sub> <strong>n</strong> </sub>, <em>n</em> = 5, 10) by anchoring a redox-active ferrocene (Fc) motif to a self-assembling peptide segment (<sup> <em>N</em> </sup>VFFAKK<sup> <em>C</em> </sup>) via methylene spacers (<em>n</em>). These nanofibers are dynamically cross-linked with a thermoresponsive polymer, <strong>P</strong> <sub> <strong>DMA</strong> </sub>, via Schiff-base chemistry to furnish <strong>Fc</strong> <sub> <strong>n</strong> </sub>-<strong>P</strong> <sub> <strong>DMA</strong> </sub> hydrogels exhibiting tunable electrical conductivity, potent radical-scavenging ability, and nonlinear strain-stiffening behavior. Notably, the hydrogels display both heat- and strain-induced stiffening behavior reminiscent of fibrin networks. <em>In vitro</em> experiments show that SH-SY5Y neuroblastom
由于神经纤维中的电信号受损，神经退行性疾病构成了一个重大的全球健康挑战，但有效的再生疗法仍然有限。在这里，我们报道了一种可注射的水凝胶，它集成了固有的导电性、抗氧化能力和应变强化力学，以模拟神经外细胞基质（ECM）的关键特征并促进神经元分化。我们设计了两亲肽（Fcn, n = 5,10），通过亚甲基间隔物(n)将氧化还原活性二茂铁（Fc）基序固定在自组装肽段（NVFFAKKC）上。这些纳米纤维通过希夫碱化学与热敏聚合物PDMA动态交联，得到Fcn-PDMA水凝胶，具有可调节的导电性、强大的自由基清除能力和非线性应变硬化行为。值得注意的是，水凝胶表现出热和应变诱导的硬化行为，类似于纤维蛋白网络。体外实验表明，包封在这些水凝胶中的sh - sy5y神经母细胞瘤细胞，特别是Fc10-PDMA，表现出优异的生物相容性，抗氧化应激能力，并增强了神经突的生长。综上所述，多功能水凝胶提供了一个仿生的3D生态位，利用电、机械和氧化还原线索协同促进神经发生。
{"title":"Intrinsically Strain-Stiffening, Conductive, ROS-Scavenging Peptide–Polymer Hydrogel to Promote Neurite Outgrowth","authors":"Debasish Nath, Jahanvi Ralhan, Pallavi S. Chaubey, Manisha Nirwan, Asish Pal","doi":"10.1021/acs.biomac.6c00930","DOIUrl":"10.1021/acs.biomac.6c00930","url":null,"abstract":"<div><div>Neurodegenerative disorders pose a major global health challenge due to impaired electrical signaling in nerve fibers, yet effective regenerative therapies remain limited. Here, we report an injectable hydrogel that integrates intrinsic conductivity, antioxidative capacity, and strain-stiffening mechanics, to emulate key features of the neural extracellular matrix (ECM) and promote neuronal differentiation. We design peptide amphiphiles (<strong>Fc</strong> <sub> <strong>n</strong> </sub>, <em>n</em> = 5, 10) by anchoring a redox-active ferrocene (Fc) motif to a self-assembling peptide segment (<sup> <em>N</em> </sup>VFFAKK<sup> <em>C</em> </sup>) via methylene spacers (<em>n</em>). These nanofibers are dynamically cross-linked with a thermoresponsive polymer, <strong>P</strong> <sub> <strong>DMA</strong> </sub>, via Schiff-base chemistry to furnish <strong>Fc</strong> <sub> <strong>n</strong> </sub>-<strong>P</strong> <sub> <strong>DMA</strong> </sub> hydrogels exhibiting tunable electrical conductivity, potent radical-scavenging ability, and nonlinear strain-stiffening behavior. Notably, the hydrogels display both heat- and strain-induced stiffening behavior reminiscent of fibrin networks. <em>In vitro</em> experiments show that SH-SY5Y neuroblastoma cells encapsulated in these hydrogels, particularly <strong>Fc</strong> <sub> <strong>10</strong> </sub>-<strong>P</strong> <sub> <strong>DMA</strong> </sub>, exhibit excellent biocompatibility, resistance to oxidative stress, and enhanced neurite outgrowth. Taken together, the multifunctional hydrogels provide a biomimetic 3D niche that leverages electrical, mechanical, and redox cues to synergistically promote neurogenesis.</div></div><div>Neurodegenerative disorders pose a major global health challenge due to impaired electrical signaling in nerve fibers, yet effective regenerative therapies remain limited. Here, we report an injectable hydrogel that integrates intrinsic conductivity, antioxidative capacity, and strain-stiffening mechanics, to emulate key features of the neural extracellular matrix (ECM) and promote neuronal differentiation. We design peptide amphiphiles (<strong>Fc</strong> <sub> <strong>n</strong> </sub>, <em>n</em> = 5, 10) by anchoring a redox-active ferrocene (Fc) motif to a self-assembling peptide segment (<sup> <em>N</em> </sup>VFFAKK<sup> <em>C</em> </sup>) via methylene spacers (<em>n</em>). These nanofibers are dynamically cross-linked with a thermoresponsive polymer, <strong>P</strong> <sub> <strong>DMA</strong> </sub>, via Schiff-base chemistry to furnish <strong>Fc</strong> <sub> <strong>n</strong> </sub>-<strong>P</strong> <sub> <strong>DMA</strong> </sub> hydrogels exhibiting tunable electrical conductivity, potent radical-scavenging ability, and nonlinear strain-stiffening behavior. Notably, the hydrogels display both heat- and strain-induced stiffening behavior reminiscent of fibrin networks. <em>In vitro</em> experiments show that SH-SY5Y neuroblastom","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6074-6085"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Breast carcinoma is the most commonly diagnosed cancer and a leading cause of cancer-related death among women globally. Conventional treatments are limited by poor targeting, systemic toxicity, and susceptibility to secondary infections, highlighting the need for localized multifunctional therapeutic systems. This study aimed to develop poly(vinyl alcohol)-loaded madecassoside nanofibers (PVA@MAD) as a localized therapeutic platform for breast cancer treatment. Fabricated nanofibers exhibited spider-web-like architecture, swelling behavior, hydrophilicity, degradation, and sustained drug release (∼95% at 72 h under acidic conditions). PVA@MAD showed cytotoxicity against MDA-MB-231 cells, with an IC50 value of 49.31 ± 0.010 μg/mL, inducing ROS-mediated apoptosis and inhibiting cell migration, indicating antimetastatic potential. In addition, the nanofibers showed antibacterial activity against Staphylococcus aureus and Escherichia coli. Hemocompatibility, brine shrimp, acute, and subacute toxicity studies confirmed excellent biocompatibility. Overall, PVA@MAD nanofibers offer a promising localized therapeutic approach combining anticancer and antibacterial activities for improved breast cancer management.
Breast carcinoma is the most commonly diagnosed cancer and a leading cause of cancer-related death among women globally. Conventional treatments are limited by poor targeting, systemic toxicity, and susceptibility to secondary infections, highlighting the need for localized multifunctional therapeutic systems. This study aimed to develop poly(vinyl alcohol)-loaded madecassoside nanofibers (PVA@MAD) as a localized therapeutic platform for breast cancer treatment. Fabricated nanofibers exhibited spider-web-like architecture, swelling behavior, hydrophilicity, degradation, and sustained drug release (∼95% at 72 h under acidic conditions). PVA@MAD showed cytotoxicity against MDA-MB-231 cells, with an IC50 value of 49.31 ± 0.010 μg/mL, inducing ROS-mediated apoptosis and inhibiting cell migration, indicating antimetastatic potential. In addition, the nanofibers showed antibacterial activity against Staphylococcus aureus and Escherichia coli. Hemocompatibility, brine shrimp, acute, and subacute toxicity studies confirmed excellent biocompatibility. Overall, PVA@MAD nanofibers offer a promising localized therapeutic approach combining anticancer and antibacterial activities for improved breast cancer management.
{"title":"Designing Single-Molecule Nanofiber Therapeutics for Breast Cancer and Biofilm Suppression","authors":"Aishwarya Jayakumar, Arjun Velusamy, Karuppuchamy Subbian, Suganthy Natarajan","doi":"10.1021/acs.biomac.6c00696","DOIUrl":"10.1021/acs.biomac.6c00696","url":null,"abstract":"<div><div>Breast carcinoma is the most commonly diagnosed cancer and a leading cause of cancer-related death among women globally. Conventional treatments are limited by poor targeting, systemic toxicity, and susceptibility to secondary infections, highlighting the need for localized multifunctional therapeutic systems. This study aimed to develop poly(vinyl alcohol)-loaded madecassoside nanofibers (PVA@MAD) as a localized therapeutic platform for breast cancer treatment. Fabricated nanofibers exhibited spider-web-like architecture, swelling behavior, hydrophilicity, degradation, and sustained drug release (∼95% at 72 h under acidic conditions). PVA@MAD showed cytotoxicity against MDA-MB-231 cells, with an IC<sub>50</sub> value of 49.31 ± 0.010 μg/mL, inducing ROS-mediated apoptosis and inhibiting cell migration, indicating antimetastatic potential. In addition, the nanofibers showed antibacterial activity against Staphylococcus aureus and Escherichia coli. Hemocompatibility, brine shrimp, acute, and subacute toxicity studies confirmed excellent biocompatibility. Overall, PVA@MAD nanofibers offer a promising localized therapeutic approach combining anticancer and antibacterial activities for improved breast cancer management.</div></div><div>Breast carcinoma is the most commonly diagnosed cancer and a leading cause of cancer-related death among women globally. Conventional treatments are limited by poor targeting, systemic toxicity, and susceptibility to secondary infections, highlighting the need for localized multifunctional therapeutic systems. This study aimed to develop poly(vinyl alcohol)-loaded madecassoside nanofibers (PVA@MAD) as a localized therapeutic platform for breast cancer treatment. Fabricated nanofibers exhibited spider-web-like architecture, swelling behavior, hydrophilicity, degradation, and sustained drug release (∼95% at 72 h under acidic conditions). PVA@MAD showed cytotoxicity against MDA-MB-231 cells, with an IC<sub>50</sub> value of 49.31 ± 0.010 μg/mL, inducing ROS-mediated apoptosis and inhibiting cell migration, indicating antimetastatic potential. In addition, the nanofibers showed antibacterial activity against Staphylococcus aureus and Escherichia coli. Hemocompatibility, brine shrimp, acute, and subacute toxicity studies confirmed excellent biocompatibility. Overall, PVA@MAD nanofibers offer a promising localized therapeutic approach combining anticancer and antibacterial activities for improved breast cancer management.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (247KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (247KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5958-5975"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noninvasive transdermal drug delivery (TDD) offers sustained therapeutic release but is hindered by the stratum corneum (SC) barrier. Herein, we report ultrasmall polymeric micelles (PMs) embedded in poly(vinyl alcohol) hydrogels for the passive TDD of rosiglitazone (RGT) to treat Type 2 diabetes mellitus (T2DM). We synthesized amphiphilic brush copolymers with varied hydrophobic cores (linear alkanes, benzene, borneol) to tune SC interactions and ensure colloidal stability. Ex vivo murine skin studies demonstrated that PM variants with C10 alkane and benzene cores achieved 10.56% and 19.84% cumulative permeation at 24 h, respectively, via dual paracellular/intracellular routes. In vivo, PM hydrogels delivered steady plasma accumulation. In a T2DM model, transdermal RGT reduced blood glucose by 30% over 12 days without observable skin or organ toxicity. This nanoplatform enables noninvasive systemic delivery, offering a robust alternative to oral administration for sustained glycemic control.
Noninvasive transdermal drug delivery (TDD) offers sustained therapeutic release but is hindered by the stratum corneum (SC) barrier. Herein, we report ultrasmall polymeric micelles (PMs) embedded in poly(vinyl alcohol) hydrogels for the passive TDD of rosiglitazone (RGT) to treat Type 2 diabetes mellitus (T2DM). We synthesized amphiphilic brush copolymers with varied hydrophobic cores (linear alkanes, benzene, borneol) to tune SC interactions and ensure colloidal stability. Ex vivo murine skin studies demonstrated that PM variants with C10 alkane and benzene cores achieved 10.56% and 19.84% cumulative permeation at 24 h, respectively, via dual paracellular/intracellular routes. In vivo, PM hydrogels delivered steady plasma accumulation. In a T2DM model, transdermal RGT reduced blood glucose by 30% over 12 days without observable skin or organ toxicity. This nanoplatform enables noninvasive systemic delivery, offering a robust alternative to oral administration for sustained glycemic control.
{"title":"Ultrasmall Polymeric Micelles Enable Noninvasive Transdermal Rosiglitazone Delivery via Lipid Fluidization and Transcytosis","authors":"Yuan Wang, Songmei Luo, Lu Wang, Yansong Zhang, Ruhui Yang, Yuhao Jiang, Jingjing Guo, Xingjie Zan, Sicheng Tang, Kejun Cheng","doi":"10.1021/acs.biomac.6c00656","DOIUrl":"10.1021/acs.biomac.6c00656","url":null,"abstract":"<div><div>Noninvasive transdermal drug delivery (TDD) offers sustained therapeutic release but is hindered by the stratum corneum (SC) barrier. Herein, we report ultrasmall polymeric micelles (PMs) embedded in poly(vinyl alcohol) hydrogels for the passive TDD of rosiglitazone (RGT) to treat Type 2 diabetes mellitus (T2DM). We synthesized amphiphilic brush copolymers with varied hydrophobic cores (linear alkanes, benzene, borneol) to tune SC interactions and ensure colloidal stability. Ex vivo murine skin studies demonstrated that PM variants with C10 alkane and benzene cores achieved 10.56% and 19.84% cumulative permeation at 24 h, respectively, via dual paracellular/intracellular routes. In vivo, PM hydrogels delivered steady plasma accumulation. In a T2DM model, transdermal RGT reduced blood glucose by 30% over 12 days without observable skin or organ toxicity. This nanoplatform enables noninvasive systemic delivery, offering a robust alternative to oral administration for sustained glycemic control.</div></div><div>Noninvasive transdermal drug delivery (TDD) offers sustained therapeutic release but is hindered by the stratum corneum (SC) barrier. Herein, we report ultrasmall polymeric micelles (PMs) embedded in poly(vinyl alcohol) hydrogels for the passive TDD of rosiglitazone (RGT) to treat Type 2 diabetes mellitus (T2DM). We synthesized amphiphilic brush copolymers with varied hydrophobic cores (linear alkanes, benzene, borneol) to tune SC interactions and ensure colloidal stability. Ex vivo murine skin studies demonstrated that PM variants with C10 alkane and benzene cores achieved 10.56% and 19.84% cumulative permeation at 24 h, respectively, via dual paracellular/intracellular routes. In vivo, PM hydrogels delivered steady plasma accumulation. In a T2DM model, transdermal RGT reduced blood glucose by 30% over 12 days without observable skin or organ toxicity. This nanoplatform enables noninvasive systemic delivery, offering a robust alternative to oral administration for sustained glycemic control.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (130KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (130KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5934-5947"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-09-14Epub Date: 2026-09-17DOI: 10.1021/acs.biomac.5c02333
Junbo Dang, Panqi Sun, Junhui Jiang, Tianhao Zhao, Ruifu Lv, Hongbo Wang, Minna Ma, Dahui Sun, Mei Zhang
Preventing tumor recurrence while promoting bone regeneration remains a major challenge for osteosarcoma implants after limb-salvage surgery. Herein, we developed a DNA molecular robot (DMR) that converts tumor microenvironment (TME) and near-infrared (NIR) stimuli into integrin-mediated mechanical forces, generating microtubule-targeting activity without drugs. The DNA–polypeptide chimera contains RGD peptides for integrin anchoring and allosteric DNA switches with tunable piconewton sensitivity. Under acidic TME and NIR irradiation, DMR modulates microtubule dynamics, suppresses adhesion protein expression through the FAK–Src pathway, and disrupts mitotic spindle formation. Consequently, DMR selectively eliminates osteosarcoma cells, reducing tumor volume by 81.5%, while simultaneously enhancing bone regeneration with a 2.1-fold increase in trabecular thickness. By transducing integrin-mediated forces into intracellular microtubule regulation, DMR provides a nonpharmacological strategy for dual-functional implants with synergistic antitumor and osteogenic activities.
Preventing tumor recurrence while promoting bone regeneration remains a major challenge for osteosarcoma implants after limb-salvage surgery. Herein, we developed a DNA molecular robot (DMR) that converts tumor microenvironment (TME) and near-infrared (NIR) stimuli into integrin-mediated mechanical forces, generating microtubule-targeting activity without drugs. The DNA–polypeptide chimera contains RGD peptides for integrin anchoring and allosteric DNA switches with tunable piconewton sensitivity. Under acidic TME and NIR irradiation, DMR modulates microtubule dynamics, suppresses adhesion protein expression through the FAK–Src pathway, and disrupts mitotic spindle formation. Consequently, DMR selectively eliminates osteosarcoma cells, reducing tumor volume by 81.5%, while simultaneously enhancing bone regeneration with a 2.1-fold increase in trabecular thickness. By transducing integrin-mediated forces into intracellular microtubule regulation, DMR provides a nonpharmacological strategy for dual-functional implants with synergistic antitumor and osteogenic activities.
{"title":"DNA Molecular Robot for Osteosarcoma Therapy and Bone Regeneration","authors":"Junbo Dang, Panqi Sun, Junhui Jiang, Tianhao Zhao, Ruifu Lv, Hongbo Wang, Minna Ma, Dahui Sun, Mei Zhang","doi":"10.1021/acs.biomac.5c02333","DOIUrl":"10.1021/acs.biomac.5c02333","url":null,"abstract":"<div><div>Preventing tumor recurrence while promoting bone regeneration remains a major challenge for osteosarcoma implants after limb-salvage surgery. Herein, we developed a DNA molecular robot (DMR) that converts tumor microenvironment (TME) and near-infrared (NIR) stimuli into integrin-mediated mechanical forces, generating microtubule-targeting activity without drugs. The DNA–polypeptide chimera contains RGD peptides for integrin anchoring and allosteric DNA switches with tunable piconewton sensitivity. Under acidic TME and NIR irradiation, DMR modulates microtubule dynamics, suppresses adhesion protein expression through the FAK–Src pathway, and disrupts mitotic spindle formation. Consequently, DMR selectively eliminates osteosarcoma cells, reducing tumor volume by 81.5%, while simultaneously enhancing bone regeneration with a 2.1-fold increase in trabecular thickness. By transducing integrin-mediated forces into intracellular microtubule regulation, DMR provides a nonpharmacological strategy for dual-functional implants with synergistic antitumor and osteogenic activities.</div></div><div>Preventing tumor recurrence while promoting bone regeneration remains a major challenge for osteosarcoma implants after limb-salvage surgery. Herein, we developed a DNA molecular robot (DMR) that converts tumor microenvironment (TME) and near-infrared (NIR) stimuli into integrin-mediated mechanical forces, generating microtubule-targeting activity without drugs. The DNA–polypeptide chimera contains RGD peptides for integrin anchoring and allosteric DNA switches with tunable piconewton sensitivity. Under acidic TME and NIR irradiation, DMR modulates microtubule dynamics, suppresses adhesion protein expression through the FAK–Src pathway, and disrupts mitotic spindle formation. Consequently, DMR selectively eliminates osteosarcoma cells, reducing tumor volume by 81.5%, while simultaneously enhancing bone regeneration with a 2.1-fold increase in trabecular thickness. By transducing integrin-mediated forces into intracellular microtubule regulation, DMR provides a nonpharmacological strategy for dual-functional implants with synergistic antitumor and osteogenic activities.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (99KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (99KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5861-5877"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-09-14Epub Date: 2026-08-12DOI: 10.1021/acs.biomac.6c01145
Nastaran Zoghi, Lu Shin Wong, Mohammed Jamali, Lee A. Fielding, Aline F. Miller, Alberto Saiani
Self-assembling peptides (SAPs) provide a versatile, biocompatible platform for soft biomaterials, but their application in mechanically robust, processable polymers remains limited. We report a peptide–polyethylene glycol (PEG) multiblock copolymer (MBCP) using the amphipathic β-sheet-forming SAP K(FEFK)2K as a physical cross-linker. Synthesized via copper-free strain-promoted azide–alkyne cycloaddition (SPAAC), the MBCP was solution-cast from water into free-standing films whose properties were governed by the peptide’s ability to form stable β-sheet fibers and aggregates. Films were tough and plastic at room temperature, but elastomeric above PEG’s melting point (>60 °C). At high temperature, a micro- and nano-scale phase-separated morphology emerged, with peptide fiber-rich domains embedded in a soft, amorphous PEG matrix. At room temperature, only microphase separation persisted, while PEG crystallization produced a semicrystalline matrix in which peptide fibers restricted large crystal growth and were likely segregated at crystallite interfaces. Extensive mechanical testing revealed resilient films with shape-recovery behavior.
Self-assembling peptides (SAPs) provide a versatile, biocompatible platform for soft biomaterials, but their application in mechanically robust, processable polymers remains limited. We report a peptide–polyethylene glycol (PEG) multiblock copolymer (MBCP) using the amphipathic β-sheet-forming SAP K(FEFK)2K as a physical cross-linker. Synthesized via copper-free strain-promoted azide–alkyne cycloaddition (SPAAC), the MBCP was solution-cast from water into free-standing films whose properties were governed by the peptide’s ability to form stable β-sheet fibers and aggregates. Films were tough and plastic at room temperature, but elastomeric above PEG’s melting point (>60 °C). At high temperature, a micro- and nano-scale phase-separated morphology emerged, with peptide fiber-rich domains embedded in a soft, amorphous PEG matrix. At room temperature, only microphase separation persisted, while PEG crystallization produced a semicrystalline matrix in which peptide fibers restricted large crystal growth and were likely segregated at crystallite interfaces. Extensive mechanical testing revealed resilient films with shape-recovery behavior.
{"title":"Design and Characterization of Self-Assembling Peptide (SAP)–Polyethylene Glycol (PEG) Multiblock Copolymers (MBCP) Thin Films","authors":"Nastaran Zoghi, Lu Shin Wong, Mohammed Jamali, Lee A. Fielding, Aline F. Miller, Alberto Saiani","doi":"10.1021/acs.biomac.6c01145","DOIUrl":"10.1021/acs.biomac.6c01145","url":null,"abstract":"<div><div>Self-assembling peptides (SAPs) provide a versatile, biocompatible platform for soft biomaterials, but their application in mechanically robust, processable polymers remains limited. We report a peptide–polyethylene glycol (PEG) multiblock copolymer (MBCP) using the amphipathic β-sheet-forming SAP K(FEFK)<sub>2</sub>K as a physical cross-linker. Synthesized via copper-free strain-promoted azide–alkyne cycloaddition (SPAAC), the MBCP was solution-cast from water into free-standing films whose properties were governed by the peptide’s ability to form stable β-sheet fibers and aggregates. Films were tough and plastic at room temperature, but elastomeric above PEG’s melting point (>60 °C). At high temperature, a micro- and nano-scale phase-separated morphology emerged, with peptide fiber-rich domains embedded in a soft, amorphous PEG matrix. At room temperature, only microphase separation persisted, while PEG crystallization produced a semicrystalline matrix in which peptide fibers restricted large crystal growth and were likely segregated at crystallite interfaces. Extensive mechanical testing revealed resilient films with shape-recovery behavior.</div></div><div>Self-assembling peptides (SAPs) provide a versatile, biocompatible platform for soft biomaterials, but their application in mechanically robust, processable polymers remains limited. We report a peptide–polyethylene glycol (PEG) multiblock copolymer (MBCP) using the amphipathic β-sheet-forming SAP K(FEFK)<sub>2</sub>K as a physical cross-linker. Synthesized via copper-free strain-promoted azide–alkyne cycloaddition (SPAAC), the MBCP was solution-cast from water into free-standing films whose properties were governed by the peptide’s ability to form stable β-sheet fibers and aggregates. Films were tough and plastic at room temperature, but elastomeric above PEG’s melting point (>60 °C). At high temperature, a micro- and nano-scale phase-separated morphology emerged, with peptide fiber-rich domains embedded in a soft, amorphous PEG matrix. At room temperature, only microphase separation persisted, while PEG crystallization produced a semicrystalline matrix in which peptide fibers restricted large crystal growth and were likely segregated at crystallite interfaces. Extensive mechanical testing revealed resilient films with shape-recovery behavior.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (119KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (119KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6143-6155"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>Peptide self-assembly and liquid–liquid phase separation (LLPS), often mediated by intrinsically disordered regions (IDRs), are natural mechanisms that translate protein molecular features into complex nano- and mesoscale architectures. Although the thermodynamics and kinetics of these processes are well understood, synthetic materials integrating both functionalities remain rare. Inspired by the conserved IDR–assembly domain (AD) architecture of amyloidogenic proteins, we hypothesized that modular recombinant constructs combining LLPS-capable IDRs with β-sheet-forming ADs could generate materials with tunable structural properties. To test this, we engineered a library of elastin-like polypeptides (ELPs) fused to amphiphilic anionic or cationic amyloidogenic peptides, enabling systematic investigation of how sequence parametersincluding ELP length, AD charge, and hydrophilicityand environmental conditions, including temperature, pH, and salt concentration, influence material behavior. Our results reveal links between molecular design and emergent multiscale structures, including micelles and vesicles embedded within coacervates. This work provides a framework for designing hybrid proteins coupling LLPS and self-assembly.</div></div><div>Peptide self-assembly and liquid–liquid phase separation (LLPS), often mediated by intrinsically disordered regions (IDRs), are natural mechanisms that translate protein molecular features into complex nano- and mesoscale architectures. Although the thermodynamics and kinetics of these processes are well understood, synthetic materials integrating both functionalities remain rare. Inspired by the conserved IDR–assembly domain (AD) architecture of amyloidogenic proteins, we hypothesized that modular recombinant constructs combining LLPS-capable IDRs with β-sheet-forming ADs could generate materials with tunable structural properties. To test this, we engineered a library of elastin-like polypeptides (ELPs) fused to amphiphilic anionic or cationic amyloidogenic peptides, enabling systematic investigation of how sequence parametersincluding ELP length, AD charge, and hydrophilicityand environmental conditions, including temperature, pH, and salt concentration, influence material behavior. Our results reveal links between molecular design and emergent multiscale structures, including micelles and vesicles embedded within coacervates. This work provides a framework for designing hybrid proteins coupling LLPS and self-assembly.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></spa
{"title":"Temperature-Triggered Nanoscale Morphological Transitions in a Synthetic Intrinsically Disordered Protein","authors":"Yulia Shmidov, Lixin Fan, Max Ney, Sonal Deshpande, Parul Sirohi, Joshua J Milligan, Ashutosh Chilkoti","doi":"10.1021/acs.biomac.6c00295","DOIUrl":"10.1021/acs.biomac.6c00295","url":null,"abstract":"<div><div>Peptide self-assembly and liquid–liquid phase separation (LLPS), often mediated by intrinsically disordered regions (IDRs), are natural mechanisms that translate protein molecular features into complex nano- and mesoscale architectures. Although the thermodynamics and kinetics of these processes are well understood, synthetic materials integrating both functionalities remain rare. Inspired by the conserved IDR–assembly domain (AD) architecture of amyloidogenic proteins, we hypothesized that modular recombinant constructs combining LLPS-capable IDRs with β-sheet-forming ADs could generate materials with tunable structural properties. To test this, we engineered a library of elastin-like polypeptides (ELPs) fused to amphiphilic anionic or cationic amyloidogenic peptides, enabling systematic investigation of how sequence parametersincluding ELP length, AD charge, and hydrophilicityand environmental conditions, including temperature, pH, and salt concentration, influence material behavior. Our results reveal links between molecular design and emergent multiscale structures, including micelles and vesicles embedded within coacervates. This work provides a framework for designing hybrid proteins coupling LLPS and self-assembly.</div></div><div>Peptide self-assembly and liquid–liquid phase separation (LLPS), often mediated by intrinsically disordered regions (IDRs), are natural mechanisms that translate protein molecular features into complex nano- and mesoscale architectures. Although the thermodynamics and kinetics of these processes are well understood, synthetic materials integrating both functionalities remain rare. Inspired by the conserved IDR–assembly domain (AD) architecture of amyloidogenic proteins, we hypothesized that modular recombinant constructs combining LLPS-capable IDRs with β-sheet-forming ADs could generate materials with tunable structural properties. To test this, we engineered a library of elastin-like polypeptides (ELPs) fused to amphiphilic anionic or cationic amyloidogenic peptides, enabling systematic investigation of how sequence parametersincluding ELP length, AD charge, and hydrophilicityand environmental conditions, including temperature, pH, and salt concentration, influence material behavior. Our results reveal links between molecular design and emergent multiscale structures, including micelles and vesicles embedded within coacervates. This work provides a framework for designing hybrid proteins coupling LLPS and self-assembly.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></spa","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5898-5907"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-09-14Epub Date: 2026-08-28DOI: 10.1021/acs.biomac.6c00682
Cheng Tang, Manni Li, Yaling Wang, Ming Zhu, Lihua Bai
<div><div>Unconventional fluorescent polymers exhibiting multicolor emission have garnered significant interest due to their unique optical properties and broad applications in bioimaging, chemical sensing, and security encryption. In this study, a series of multicolor fluorescent aliphatic hyperbranched polyphosphate esters were synthesized from a natural product. The prepared polymers demonstrated notable red emission, excitation-dependent fluorescence, concentration-enhanced luminescence, and aggregation-induced red-shifted emission. Experimental data combined with theoretical calculations revealed that intermolecular and intramolecular interactions promoted molecular aggregation, thereby enhancing n-π interactions. These strengthened n-π interactions further facilitated spatial electronic communication, leading to prominent multicolor fluorescence. The balance between hydroxyl and triethyl phosphate groups within the polymers promoted aggregation and spatial electronic communication, resulting in longer wavelength emission. Studies showed that the electrostatic potential distribution of the polymers played an important role in regulating their emission properties. Moreover, these polymers were successfully applied in ion sensing and fluorescent hydrogel preparation. This work provides new insights into the emission mechanism of unconventional fluorescent polymers.</div></div><div>Unconventional fluorescent polymers exhibiting multicolor emission have garnered significant interest due to their unique optical properties and broad applications in bioimaging, chemical sensing, and security encryption. In this study, a series of multicolor fluorescent aliphatic hyperbranched polyphosphate esters were synthesized from a natural product. The prepared polymers demonstrated notable red emission, excitation-dependent fluorescence, concentration-enhanced luminescence, and aggregation-induced red-shifted emission. Experimental data combined with theoretical calculations revealed that intermolecular and intramolecular interactions promoted molecular aggregation, thereby enhancing n-π interactions. These strengthened n-π interactions further facilitated spatial electronic communication, leading to prominent multicolor fluorescence. The balance between hydroxyl and triethyl phosphate groups within the polymers promoted aggregation and spatial electronic communication, resulting in longer wavelength emission. Studies showed that the electrostatic potential distribution of the polymers played an important role in regulating their emission properties. Moreover, these polymers were successfully applied in ion sensing and fluorescent hydrogel preparation. This work provides new insights into the emission mechanism of unconventional fluorescent polymers.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (176KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></
{"title":"Unconventional Multicolor Fluorescent Aliphatic Hyperbranched Polyphosphate Esters with Enhanced Spatial Electronic Communication for Ion Detection and Fluorescent Hydrogel Fabrication","authors":"Cheng Tang, Manni Li, Yaling Wang, Ming Zhu, Lihua Bai","doi":"10.1021/acs.biomac.6c00682","DOIUrl":"10.1021/acs.biomac.6c00682","url":null,"abstract":"<div><div>Unconventional fluorescent polymers exhibiting multicolor emission have garnered significant interest due to their unique optical properties and broad applications in bioimaging, chemical sensing, and security encryption. In this study, a series of multicolor fluorescent aliphatic hyperbranched polyphosphate esters were synthesized from a natural product. The prepared polymers demonstrated notable red emission, excitation-dependent fluorescence, concentration-enhanced luminescence, and aggregation-induced red-shifted emission. Experimental data combined with theoretical calculations revealed that intermolecular and intramolecular interactions promoted molecular aggregation, thereby enhancing n-π interactions. These strengthened n-π interactions further facilitated spatial electronic communication, leading to prominent multicolor fluorescence. The balance between hydroxyl and triethyl phosphate groups within the polymers promoted aggregation and spatial electronic communication, resulting in longer wavelength emission. Studies showed that the electrostatic potential distribution of the polymers played an important role in regulating their emission properties. Moreover, these polymers were successfully applied in ion sensing and fluorescent hydrogel preparation. This work provides new insights into the emission mechanism of unconventional fluorescent polymers.</div></div><div>Unconventional fluorescent polymers exhibiting multicolor emission have garnered significant interest due to their unique optical properties and broad applications in bioimaging, chemical sensing, and security encryption. In this study, a series of multicolor fluorescent aliphatic hyperbranched polyphosphate esters were synthesized from a natural product. The prepared polymers demonstrated notable red emission, excitation-dependent fluorescence, concentration-enhanced luminescence, and aggregation-induced red-shifted emission. Experimental data combined with theoretical calculations revealed that intermolecular and intramolecular interactions promoted molecular aggregation, thereby enhancing n-π interactions. These strengthened n-π interactions further facilitated spatial electronic communication, leading to prominent multicolor fluorescence. The balance between hydroxyl and triethyl phosphate groups within the polymers promoted aggregation and spatial electronic communication, resulting in longer wavelength emission. Studies showed that the electrostatic potential distribution of the polymers played an important role in regulating their emission properties. Moreover, these polymers were successfully applied in ion sensing and fluorescent hydrogel preparation. This work provides new insights into the emission mechanism of unconventional fluorescent polymers.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (176KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5948-5957"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号