Biomacromolecules最新文献

{"title":"Mechanistic Insights into the Formation of Complex Coacervates in Crowded Environments","authors":"Shanta Biswas,&nbsp;Sai Venkatesh Pingali,&nbsp;Katie T. Tran,&nbsp;Qingqiu Huang,&nbsp;Xiaobing Zuo,&nbsp;Amy Y. Xu","doi":"10.1021/acs.biomac.6c01306","DOIUrl":"10.1021/acs.biomac.6c01306","url":null,"abstract":"<div><div>Complex coacervates are widely used as model systems for studying biomolecular condensate formation, yet how intracellular crowding influences coacervation mechanisms remains unclear. Here, we investigate a model protein–polymer coacervate system in dilute and crowded environments to elucidate its formation mechanism. In dilute solutions, protein–polymer complexes gradually grow into larger assemblies as their net charge approaches neutrality. Under crowded conditions, excluded-volume effects force polymer chains into highly coiled conformations, creating a dense polymer network before the protein is introduced. Protein incorporation into this network relieves conformational tension and triggers the formation of protein–polymer networks that act as scaffolds for coacervates, bypassing the gradual charge-driven assembly seen under dilute conditions. Despite this mechanistic difference, crowders are found to be excluded from the dense phase, yielding comparable mesoscale structures under both conditions. Overall, this work suggests how condensates may adapt their assembly mechanisms within complex cellular environments.</div></div><div>Complex coacervates are widely used as model systems for studying biomolecular condensate formation, yet how intracellular crowding influences coacervation mechanisms remains unclear. Here, we investigate a model protein–polymer coacervate system in dilute and crowded environments to elucidate its formation mechanism. In dilute solutions, protein–polymer complexes gradually grow into larger assemblies as their net charge approaches neutrality. Under crowded conditions, excluded-volume effects force polymer chains into highly coiled conformations, creating a dense polymer network before the protein is introduced. Protein incorporation into this network relieves conformational tension and triggers the formation of protein–polymer networks that act as scaffolds for coacervates, bypassing the gradual charge-driven assembly seen under dilute conditions. Despite this mechanistic difference, crowders are found to be excluded from the dense phase, yielding comparable mesoscale structures under both conditions. Overall, this work suggests how condensates may adapt their assembly mechanisms within complex cellular environments.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (71KB)</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 (71KB)</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 6214-6226"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958054","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}

{"title":"Dextran-Mediated Control of Ice Crystallization in Polyphenol-Protein Fibril Networks for Freeze–Thawing-Stable Hydrogels with Anti-Inflammatory Activity","authors":"Mengyao Sun,&nbsp;Hui Zhao,&nbsp;Shiqi Bai,&nbsp;Siying Cheng,&nbsp;Salvatore Assenza,&nbsp;Bing Hu","doi":"10.1021/acs.biomac.6c00906","DOIUrl":"10.1021/acs.biomac.6c00906","url":null,"abstract":"<div><div>Freeze–thawing (F–T) cycling compromises the structural integrity and functionality of biomacromolecular hydrogels due to uncontrolled water crystallization and ice-crystal growth. Herein, we identified dextran from screening different polysaccharides and synthetic polymers as an ideal ice-crystal modifier for protein amyloid fibril-polyphenol hydrogels. Formation of the ternary composite hydrogel and F–T resistance were positively dependent on dextran molecular weight and concentration, with a tolerance for exceeding 50 times F–T cycles. Low-temperature differential scanning calorimetry (DSC) and ice-crystal observation showed reduced freezable water and restricted ice growth in hydrogels, while rheology and microstructure characterization revealed enhanced strength and a denser, more uniform porous network after F–T treatment. These improvements were attributed to dextran-mediated network confinement, which imposed strong constraints on ice formation and growth. Furthermore, the hydrogel retained <em>in vitro</em> and <em>in vivo</em> anti-inflammatory activities with high biocompatibility. This work provided a polysaccharide-modulated ice templating for hydrogel engineering in bioactive delivery.</div></div><div>Freeze–thawing (F–T) cycling compromises the structural integrity and functionality of biomacromolecular hydrogels due to uncontrolled water crystallization and ice-crystal growth. Herein, we identified dextran from screening different polysaccharides and synthetic polymers as an ideal ice-crystal modifier for protein amyloid fibril-polyphenol hydrogels. Formation of the ternary composite hydrogel and F–T resistance were positively dependent on dextran molecular weight and concentration, with a tolerance for exceeding 50 times F–T cycles. Low-temperature differential scanning calorimetry (DSC) and ice-crystal observation showed reduced freezable water and restricted ice growth in hydrogels, while rheology and microstructure characterization revealed enhanced strength and a denser, more uniform porous network after F–T treatment. These improvements were attributed to dextran-mediated network confinement, which imposed strong constraints on ice formation and growth. Furthermore, the hydrogel retained <em>in vitro</em> and <em>in vivo</em> anti-inflammatory activities with high biocompatibility. This work provided a polysaccharide-modulated ice templating for hydrogel engineering in bioactive delivery.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (257KB)</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 (257KB)</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 6044-6057"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861195","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}

{"title":"Stimuli-Responsive DNA Tetrahedral Lysosome-Targeting Chimeras for Enhanced HER2 Protein Degradation","authors":"Lulu Song,&nbsp;Miaomiao Zhou,&nbsp;Ya Wang,&nbsp;Xiaoli Guo,&nbsp;Xinyi Yang,&nbsp;Yiqiong Hu,&nbsp;Yifu Wang,&nbsp;Songcheng Yu,&nbsp;Wei Liu,&nbsp;Leiliang He","doi":"10.1021/acs.biomac.6c00257","DOIUrl":"10.1021/acs.biomac.6c00257","url":null,"abstract":"<div><div>Overexpression and abnormal activation of membrane proteins promote malignant tumor cell proliferation, while traditional interventions are often limited by drug resistance caused by target mutations. Here, we designed a stimulus-responsive DNA tetrahedron lysosome-targeted chimera (tFNA-LYTAC) strategy for degrading embrane proteins. Two tetrahedra are modified with trivalent HER2 aptamers (tFNA1-Apt) and trivalent IGF2R aptamers (tFNA2-Apt), enabling targeted binding to HER2 and IGF2R, and are then self-assembled into tFNA-LYTAC under VEGF stimulation to promote HER2 degradation. The trivalent aptamer modification strategy significantly enhances the overall binding capacity of tFNA1-Apt to cells. Importantly, tFNA-LYTAC formed only in the presence of VEGF, integrating tetrahedral multivalent aptamer targeting with stimulus responsiveness to improve the degradation specificity. VEGF-responsive tFNA-LYTAC promoted HER2 degradation and suppressed the phosphorylation of key downstream signaling proteins. The study innovatively proposes a “target recognition-stimulus response-endocytic degradation” mode that selectively regulates membrane proteins through programmable multivalent aptamer nanostructures.</div></div><div>Overexpression and abnormal activation of membrane proteins promote malignant tumor cell proliferation, while traditional interventions are often limited by drug resistance caused by target mutations. Here, we designed a stimulus-responsive DNA tetrahedron lysosome-targeted chimera (tFNA-LYTAC) strategy for degrading embrane proteins. Two tetrahedra are modified with trivalent HER2 aptamers (tFNA1-Apt) and trivalent IGF2R aptamers (tFNA2-Apt), enabling targeted binding to HER2 and IGF2R, and are then self-assembled into tFNA-LYTAC under VEGF stimulation to promote HER2 degradation. The trivalent aptamer modification strategy significantly enhances the overall binding capacity of tFNA1-Apt to cells. Importantly, tFNA-LYTAC formed only in the presence of VEGF, integrating tetrahedral multivalent aptamer targeting with stimulus responsiveness to improve the degradation specificity. VEGF-responsive tFNA-LYTAC promoted HER2 degradation and suppressed the phosphorylation of key downstream signaling proteins. The study innovatively proposes a “target recognition-stimulus response-endocytic degradation” mode that selectively regulates membrane proteins through programmable multivalent aptamer nanostructures.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (138KB)</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 (138KB)</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 5887-5897"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958027","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}

{"title":"Coordination-Driven Programming of MOF Stability via Targeting Protein Corona Engineering for Hypoxia-Relieving Sonodynamic Therapy","authors":"Youjung Sim,&nbsp;Gyeongseok Yang,&nbsp;Joohan Nam,&nbsp;Seungo Baek,&nbsp;Jung Heum Yoon,&nbsp;Jinhyu Lee,&nbsp;Hong Kyu Lee,&nbsp;Jaewoo Lee,&nbsp;Eunshil Choi,&nbsp;Gun Kim,&nbsp;Wonyoung Choe,&nbsp;Ja-Hyoung Ryu","doi":"10.1021/acs.biomac.6c00899","DOIUrl":"10.1021/acs.biomac.6c00899","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Zr-based metal–organic frameworks (MOFs) are promising nanomedicine platforms, but their rapid degradation in phosphate-rich biological environments remains a critical barrier to clinical translation. Here, incorporating MnOx into the porphyrinic Zr-MOF PCN-224 modulates the coordination environment of Zr&lt;sub&gt;6&lt;/sub&gt; clusters, suppressing phosphate-induced linker displacement and extending structural integrity under physiological conditions. The optimized 1:1 MnOx@PCN-224 formulation resists phosphate-triggered disassembly and porphyrin release in phosphate-buffered saline (PBS). MnOx also acts as a catalase mimic, converting endogenous H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; into O&lt;sub&gt;2&lt;/sub&gt; to relieve tumor hypoxia and potentiate sonodynamic therapy (SDT). Under high-intensity focused ultrasound (HIFU) irradiation, stabilized porphyrin linkers generate enhanced &lt;sup&gt;1&lt;/sup&gt;O&lt;sub&gt;2&lt;/sub&gt; levels. Functionalization with GST-EGFR as a preadsorbed targeting protein corona enables tumor-specific delivery, and the resulting nanoplatform suppresses tumor growth in a 4T1 breast tumor model. This coordination-driven strategy transforms the inherent lability of Zr-MOFs into a designable parameter for engineering biointerface stability for &lt;em&gt;in vivo&lt;/em&gt; therapeutic applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Zr-based metal–organic frameworks (MOFs) are promising nanomedicine platforms, but their rapid degradation in phosphate-rich biological environments remains a critical barrier to clinical translation. Here, incorporating MnOx into the porphyrinic Zr-MOF PCN-224 modulates the coordination environment of Zr&lt;sub&gt;6&lt;/sub&gt; clusters, suppressing phosphate-induced linker displacement and extending structural integrity under physiological conditions. The optimized 1:1 MnOx@PCN-224 formulation resists phosphate-triggered disassembly and porphyrin release in phosphate-buffered saline (PBS). MnOx also acts as a catalase mimic, converting endogenous H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; into O&lt;sub&gt;2&lt;/sub&gt; to relieve tumor hypoxia and potentiate sonodynamic therapy (SDT). Under high-intensity focused ultrasound (HIFU) irradiation, stabilized porphyrin linkers generate enhanced &lt;sup&gt;1&lt;/sup&gt;O&lt;sub&gt;2&lt;/sub&gt; levels. Functionalization with GST-EGFR as a preadsorbed targeting protein corona enables tumor-specific delivery, and the resulting nanoplatform suppresses tumor growth in a 4T1 breast tumor model. This coordination-driven strategy transforms the inherent lability of Zr-MOFs into a designable parameter for engineering biointerface stability for &lt;em&gt;in vivo&lt;/em&gt; therapeutic applications.&lt;/div&gt;&lt;div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (103KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download full-size image&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ol&gt;&lt;/span&gt;&lt;/figure&gt;&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (103KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6033-6043"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958048","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}

{"title":"Tensile Stress Enhances Moisture Sorption by Increasing Cellulose Hydroxyl Accessibility in Wood Cell Walls","authors":"Fengze Sun,&nbsp;Wenjuan Zhao,&nbsp;Yujing Tan,&nbsp;Kaiwen Chen,&nbsp;Yi Kong,&nbsp;Hui Peng,&nbsp;Zhu Li,&nbsp;Jiali Jiang,&nbsp;Tianyi Zhan,&nbsp;Chi Zhang,&nbsp;Jianxiong Lyu","doi":"10.1021/acs.biomac.6c01305","DOIUrl":"10.1021/acs.biomac.6c01305","url":null,"abstract":"<div><div>Mechanical loading coupled with moisture sorption causes mechano-sorptive creep in wood, but its molecular origin remains unclear. Here, DMA, in situ tensile FTIR, SAXS/WAXS, and MD/GCMC simulations were combined to examine molecular and nanostructural changes in wood cell walls during sorption under tensile stress. Adsorption under stress produced a higher moisture content than stress-free adsorption, whereas viscoelastic creep at constant relative humidity caused no additional uptake. The enhancement was most evident when the loading was approximately parallel to cellulose microfibrils. FTIR revealed changes in cellulose hydroxyl environments consistent with increased accessibility, while SAXS/WAXS showed enlarged interfibrillar distances with nearly unchanged crystalline lattice spacings. Simulations further indicated reduced polymer–polymer hydrogen bonding, greater solvent-accessible surface area, and pore opening during simultaneous adsorption and loading. Together, these findings link tensile-stress-induced cellulose hydroxyl accessibility to enhanced moisture sorption in the wood cell walls.</div></div><div>Mechanical loading coupled with moisture sorption causes mechano-sorptive creep in wood, but its molecular origin remains unclear. Here, DMA, in situ tensile FTIR, SAXS/WAXS, and MD/GCMC simulations were combined to examine molecular and nanostructural changes in wood cell walls during sorption under tensile stress. Adsorption under stress produced a higher moisture content than stress-free adsorption, whereas viscoelastic creep at constant relative humidity caused no additional uptake. The enhancement was most evident when the loading was approximately parallel to cellulose microfibrils. FTIR revealed changes in cellulose hydroxyl environments consistent with increased accessibility, while SAXS/WAXS showed enlarged interfibrillar distances with nearly unchanged crystalline lattice spacings. Simulations further indicated reduced polymer–polymer hydrogen bonding, greater solvent-accessible surface area, and pore opening during simultaneous adsorption and loading. Together, these findings link tensile-stress-induced cellulose hydroxyl accessibility to enhanced moisture sorption in the wood cell walls.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (207KB)</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 (207KB)</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 6199-6213"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958050","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}

{"title":"Long-Lived Room-Temperature Phosphorescent Cellulose Materials with Dynamic Cross-Linking","authors":"Lei Luo,&nbsp;Huiyu Bai,&nbsp;Ting Li,&nbsp;Xuhui Zhang,&nbsp;Jing Huang,&nbsp;Shibo Wang,&nbsp;Yang Wang,&nbsp;Weifu Dong","doi":"10.1021/acs.biomac.6c01086","DOIUrl":"10.1021/acs.biomac.6c01086","url":null,"abstract":"<div><div>In this work, a multicomponent boric acid cross-linking strategy was developed to prepare cellulose-based RTP materials, using sodium carboxymethyl cellulose as the rigid matrix, poly­(vinyl alcohol) (PVA) as the auxiliary network regulator, boric acid as the dynamic covalent cross-linker, and 9-phenanthreneboronic acid (PA) as the phosphorescent guest. Boric acid forms a dynamic covalent cross-linked network with hydroxyl groups of CMC and PVA, while PA is tightly immobilized in the matrix through hydrogen bonding and boron-associated coordination interactions, constructing a dense and rigid confined microenvironment. The cellulose-based film exhibits excellent RTP performance, with a phosphorescence lifetime of 2.61 s, an absolute quantum yield of 13.85%, and a visually distinguishable afterglow lasting up to 20 s. Meanwhile, the cross-linked structure endows the material with outstanding mechanical properties (tensile strength of 140 MPa). Additionally, the material displays multiple functional characteristics, including time-resolved information encryption, water-rewritable capability, and reversible responsiveness to humidity and pH.</div></div><div>In this work, a multicomponent boric acid cross-linking strategy was developed to prepare cellulose-based RTP materials, using sodium carboxymethyl cellulose as the rigid matrix, poly­(vinyl alcohol) (PVA) as the auxiliary network regulator, boric acid as the dynamic covalent cross-linker, and 9-phenanthreneboronic acid (PA) as the phosphorescent guest. Boric acid forms a dynamic covalent cross-linked network with hydroxyl groups of CMC and PVA, while PA is tightly immobilized in the matrix through hydrogen bonding and boron-associated coordination interactions, constructing a dense and rigid confined microenvironment. The cellulose-based film exhibits excellent RTP performance, with a phosphorescence lifetime of 2.61 s, an absolute quantum yield of 13.85%, and a visually distinguishable afterglow lasting up to 20 s. Meanwhile, the cross-linked structure endows the material with outstanding mechanical properties (tensile strength of 140 MPa). Additionally, the material displays multiple functional characteristics, including time-resolved information encryption, water-rewritable capability, and reversible responsiveness to humidity and pH.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (129KB)</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 (129KB)</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 6111-6120"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958069","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}

{"title":"Mucoadhesive Carboxymethyl Chitosan Hydrogel Eyedrops via Dual Dynamic Covalent Chemistry for Long-Acting Glaucoma Therapy","authors":"Jin Pan,&nbsp;Huangkun Gong,&nbsp;Qiuyun Shao,&nbsp;Xuehan Zhang,&nbsp;Ravin Narain,&nbsp;Kaihui Nan,&nbsp;Yangjun Chen","doi":"10.1021/acs.biomac.6c00615","DOIUrl":"10.1021/acs.biomac.6c00615","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Glaucoma, a leading cause of irreversible blindness, is commonly treated with topical eye drops that reduce intraocular pressure (IOP), but their efficacy is limited by rapid precorneal clearance. To address this, we developed a dynamic hydrogel (CSFP) via Schiff base bonding between carboxymethyl chitosan (CMCS) and 4-formylphenylboronic acid (FPBA) as an advanced delivery vehicle for brimonidine (BRI) and timolol (TIM), two common IOP-lowering agents. The mechanical properties were tunable by adjusting CMCS and FPBA concentrations. The optimized hydrogel exhibited a storage modulus of ∼38.8 Pa (at 1 Hz, 1% strain), excellent self-healing ability, and shear-thinning behavior, facilitating easy administration and resistance to blink-induced clearance. It also achieved near 100% transmittance and a refractive index of 1.339, ensuring optical clarity. Notably, the incorporated phenylboronic acid (PBA) groups enabled selective binding to sialic acid residues on ocular mucins via dynamic phenylboronic ester bonding, prolonging precorneal retention beyond 30 min compared to less than 5 min for the solution control. In a magnetic bead-induced ocular hypertensive rat model, CSFP hydrogel loaded with either BRI or TIM induced greater and long-lasting IOP reduction than the free drug solutions. This work highlights the potential of mucoadhesive dynamic covalent hydrogels for advanced ocular drug delivery.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Glaucoma, a leading cause of irreversible blindness, is commonly treated with topical eye drops that reduce intraocular pressure (IOP), but their efficacy is limited by rapid precorneal clearance. To address this, we developed a dynamic hydrogel (CSFP) via Schiff base bonding between carboxymethyl chitosan (CMCS) and 4-formylphenylboronic acid (FPBA) as an advanced delivery vehicle for brimonidine (BRI) and timolol (TIM), two common IOP-lowering agents. The mechanical properties were tunable by adjusting CMCS and FPBA concentrations. The optimized hydrogel exhibited a storage modulus of ∼38.8 Pa (at 1 Hz, 1% strain), excellent self-healing ability, and shear-thinning behavior, facilitating easy administration and resistance to blink-induced clearance. It also achieved near 100% transmittance and a refractive index of 1.339, ensuring optical clarity. Notably, the incorporated phenylboronic acid (PBA) groups enabled selective binding to sialic acid residues on ocular mucins via dynamic phenylboronic ester bonding, prolonging precorneal retention beyond 30 min compared to less than 5 min for the solution control. In a magnetic bead-induced ocular hypertensive rat model, CSFP hydrogel loaded with either BRI or TIM induced greater and long-lasting IOP reduction than the free drug solutions. This work highlights the potential of mucoadhesive dynamic covalent hydrogels for advanced ocular drug delivery.&lt;/div&gt;&lt;div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (176KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5920-5933"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861194","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}

{"title":"Molecular Dynamics Simulations Suggest Folded Chain Ends Compatible with the Cellulose-II Fibril Structure","authors":"Linghan Kong,&nbsp;Stephen J. Eichhorn,&nbsp;Richard A. Bryce","doi":"10.1021/acs.biomac.6c00983","DOIUrl":"10.1021/acs.biomac.6c00983","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The structural feasibility of chain folding within an accepted cellulose-II structure is investigated in this study. We incorporate 3-residue and 5-residue folded glucosyl turns into a cellulose-II fibril crystal model to assess if the dominant structure can be retained. Ten candidate turn models were generated by metadynamics simulations and ranked by semiempirical quantum mechanical energies. Across &gt;30 independent 300 ns molecular dynamics trajectories, the crystalline core retains its unit cell parameters, X-ray diffraction pattern, hydrogen bonding network, and canonical &lt;sup&gt;4&lt;/sup&gt;C&lt;sub&gt;1&lt;/sub&gt; ring conformation. This suggests that, should such folds be present, they need not compromise bulk crystalline integrity. No significant fibril twisting was observed in either the unfolded or chain-fold models. At the chain-folding ends of the fibril, high-energy boat and skew-boat conformations drive hydroxymethyl rotamer redistribution and noncanonical hydrogen bonding contacts. The greater structural flexibility of the 5-residue folded turns allows the chain-fold ends to access a broader conformational space, yet the structural perturbation remains localized within the same 3-residue region as the 3-residue folded turns. The 3-residue turn is therefore considered the more plausible chain-fold structure for cellulose-II, should such a structure actually exist in reality.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;The structural feasibility of chain folding within an accepted cellulose-II structure is investigated in this study. We incorporate 3-residue and 5-residue folded glucosyl turns into a cellulose-II fibril crystal model to assess if the dominant structure can be retained. Ten candidate turn models were generated by metadynamics simulations and ranked by semiempirical quantum mechanical energies. Across &gt;30 independent 300 ns molecular dynamics trajectories, the crystalline core retains its unit cell parameters, X-ray diffraction pattern, hydrogen bonding network, and canonical &lt;sup&gt;4&lt;/sup&gt;C&lt;sub&gt;1&lt;/sub&gt; ring conformation. This suggests that, should such folds be present, they need not compromise bulk crystalline integrity. No significant fibril twisting was observed in either the unfolded or chain-fold models. At the chain-folding ends of the fibril, high-energy boat and skew-boat conformations drive hydroxymethyl rotamer redistribution and noncanonical hydrogen bonding contacts. The greater structural flexibility of the 5-residue folded turns allows the chain-fold ends to access a broader conformational space, yet the structural perturbation remains localized within the same 3-residue region as the 3-residue folded turns. The 3-residue turn is therefore considered the more plausible chain-fold structure for cellulose-II, should such a structure actually exist in reality.&lt;/div&gt;&lt;div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (101KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download full-siz","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6086-6095"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958025","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}

{"title":"Impact of DNA Sequence and Structure on Polyelectrolyte Complex Micelle Morphology","authors":"Aasim F. Hussain,&nbsp;Christian L. Keys,&nbsp;James T. Houston,&nbsp;Alexander E. Marras","doi":"10.1021/acs.biomac.6c00891","DOIUrl":"10.1021/acs.biomac.6c00891","url":null,"abstract":"<div><div>Polyelectrolyte complex micelles (PCMs) are promising nucleic acid nanocarriers; however, nucleic acids are usually treated as generic polyanions, leaving the impact of nucleotide sequence and partially hybridized structures unclear. Here, we systematically tune DNA stiffness in PCMs using (i) single-stranded sequences with varied purine contents and (ii) hybridization structures in the form of hairpins, single-tailed duplexes, and double-tailed duplexes. Small-angle X-ray scattering, electron microscopy, and dynamic light scattering reveal a strong bending penalty imposed by increasing DNA stiffness that drives a transition from spherical to less-curved cylindrical or worm-like PCMs with ordered cores. Increasing the purine content produces gradual morphological changes, whereas hybridized constructs show sharper transitions. We further link the availability of base-stacking sites to the cylindrical PCM length and see that longer rigid DNA results in higher stiffness of cylindrical PCMs. The results establish relationships connecting the DNA sequence, structure, and polymer length to PCM morphology.</div></div><div>Polyelectrolyte complex micelles (PCMs) are promising nucleic acid nanocarriers; however, nucleic acids are usually treated as generic polyanions, leaving the impact of nucleotide sequence and partially hybridized structures unclear. Here, we systematically tune DNA stiffness in PCMs using (i) single-stranded sequences with varied purine contents and (ii) hybridization structures in the form of hairpins, single-tailed duplexes, and double-tailed duplexes. Small-angle X-ray scattering, electron microscopy, and dynamic light scattering reveal a strong bending penalty imposed by increasing DNA stiffness that drives a transition from spherical to less-curved cylindrical or worm-like PCMs with ordered cores. Increasing the purine content produces gradual morphological changes, whereas hybridized constructs show sharper transitions. We further link the availability of base-stacking sites to the cylindrical PCM length and see that longer rigid DNA results in higher stiffness of cylindrical PCMs. The results establish relationships connecting the DNA sequence, structure, and polymer length to PCM morphology.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (57KB)</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 (57KB)</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 6023-6032"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958042","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}

{"title":"Contrast Agent Design to Deliver Improved Ultrasound Echogenicity from Medical Devices: A Route to In-Ward Device Placement Tracking","authors":"Amy Stimpson,&nbsp;Jerry Contreras,&nbsp;Bryce Roper,&nbsp;James W. Caruana,&nbsp;Ifty Ahmed,&nbsp;Cordula Hege,&nbsp;Joseph Sefton,&nbsp;Abby R. Whittington,&nbsp;Derek J. Irvine","doi":"10.1021/acs.biomac.6c00731","DOIUrl":"10.1021/acs.biomac.6c00731","url":null,"abstract":"&lt;div&gt;&lt;div&gt;This work reports a scalable strategy for producing polymeric medical devices with enhanced ultrasound (US) echogenicity via tailored dispersant design to support safer image-guided medical device placement. Real-time US imaging offers an alternative to X-ray imaging, reducing radiation exposure while enabling accurate device positioning/monitoring. Previous studies showed that including bioabsorbable phosphate-based glass (PBG) microspheres into thermoplastic polyurethane (TPU) could improve echogenicity. However, aggregation and processing defects limited the performance. To address this, two classes of acid-functionalized dispersants were synthesized to improve the microsphere dispersion and compatibility with TPU. These, i.e., dodecenylsuccinic diacid (DDSD) and oligomeric methacrylate/acrylates prepared using acid-functionalized chain-transfer agents, were grafted onto PBG microspheres via dip-coating and thermal treatment. Successful surface modification was confirmed by separation testing, SEM, and XPS. TPU composites containing the coated microspheres were then extruded into catheter-like structures and shown to demonstrate enhanced, more uniform echogenicity under clinical US imaging conditions without compromising the mechanical properties.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;This work reports a scalable strategy for producing polymeric medical devices with enhanced ultrasound (US) echogenicity via tailored dispersant design to support safer image-guided medical device placement. Real-time US imaging offers an alternative to X-ray imaging, reducing radiation exposure while enabling accurate device positioning/monitoring. Previous studies showed that including bioabsorbable phosphate-based glass (PBG) microspheres into thermoplastic polyurethane (TPU) could improve echogenicity. However, aggregation and processing defects limited the performance. To address this, two classes of acid-functionalized dispersants were synthesized to improve the microsphere dispersion and compatibility with TPU. These, i.e., dodecenylsuccinic diacid (DDSD) and oligomeric methacrylate/acrylates prepared using acid-functionalized chain-transfer agents, were grafted onto PBG microspheres via dip-coating and thermal treatment. Successful surface modification was confirmed by separation testing, SEM, and XPS. TPU composites containing the coated microspheres were then extruded into catheter-like structures and shown to demonstrate enhanced, more uniform echogenicity under clinical US imaging conditions without compromising the mechanical properties.&lt;/div&gt;&lt;div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (104KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download full-size image&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ol&gt;&lt;/span&gt;&lt;/figure&gt;&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (104KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download full-size ima","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5984-5996"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958070","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}