Chandrashish Roy, Priya Banerjee and Sourabh Ghosh
Advancements in 3D bioprinting demand bioinks that demonstrate not only precise printability and mechanical robustness but also consistent biochemical and cellular performance. From previous iterations in our laboratory, a silk fibroin–gelatin (SF–G) bioink was conjugated with mushroom tyrosinase (MT) as the enzymatic crosslinker. However, its clinical translation was hindered by several limitations, including batch-to-batch variation in concentration and enzymatic activity, protracted gelation kinetics, and inconsistent rheological and structural characteristics. To overcome these challenges, we developed a next-generation SF–G bioink employing horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as an alternative enzymatic crosslinking system. This approach facilitated rapid and tunable crosslinking through β-sheet enhancement, yielding hydrogels with improved stiffness, shape fidelity, and resistance to enzymatic degradation. Detailed rheological analysis confirmed optimal shear-thinning behaviour and print fidelity, while reactive oxygen species (ROS) quantification ensured cytocompatibility across physiologically relevant concentrations. Human bone marrow-derived mesenchymal stem cells (hBMSCs) encapsulated within the constructs maintained high viability and demonstrated robust osteogenic and chondrogenic lineage commitment. Furthermore, supplementation with triiodothyronine (T3) and transforming growth factor-β3 (TGF-β3) augmented matrix deposition and tissue-specific morphogenesis. Notably, a 10 U HRP–H2O2 formulation emerged as the most promising candidate, offering a strategic balance of mechanical integrity, bioactivity, and reproducibility. This optimized enzymatic system paves the way for scalable and clinically viable SF–G bioinks tailored for advanced tissue engineering and regenerative medicine applications.
{"title":"HRP-crosslinked silk–gelatin bioinks: printability dynamics and modulation of stem cell lineage commitment in 3D bioprinted constructs","authors":"Chandrashish Roy, Priya Banerjee and Sourabh Ghosh","doi":"10.1039/D6TB00628K","DOIUrl":"10.1039/D6TB00628K","url":null,"abstract":"<p >Advancements in 3D bioprinting demand bioinks that demonstrate not only precise printability and mechanical robustness but also consistent biochemical and cellular performance. From previous iterations in our laboratory, a silk fibroin–gelatin (SF–G) bioink was conjugated with mushroom tyrosinase (MT) as the enzymatic crosslinker. However, its clinical translation was hindered by several limitations, including batch-to-batch variation in concentration and enzymatic activity, protracted gelation kinetics, and inconsistent rheological and structural characteristics. To overcome these challenges, we developed a next-generation SF–G bioink employing horseradish peroxidase (HRP) and hydrogen peroxide (H<small><sub>2</sub></small>O<small><sub>2</sub></small>) as an alternative enzymatic crosslinking system. This approach facilitated rapid and tunable crosslinking through β-sheet enhancement, yielding hydrogels with improved stiffness, shape fidelity, and resistance to enzymatic degradation. Detailed rheological analysis confirmed optimal shear-thinning behaviour and print fidelity, while reactive oxygen species (ROS) quantification ensured cytocompatibility across physiologically relevant concentrations. Human bone marrow-derived mesenchymal stem cells (hBMSCs) encapsulated within the constructs maintained high viability and demonstrated robust osteogenic and chondrogenic lineage commitment. Furthermore, supplementation with triiodothyronine (T3) and transforming growth factor-β3 (TGF-β3) augmented matrix deposition and tissue-specific morphogenesis. Notably, a 10 U HRP–H<small><sub>2</sub></small>O<small><sub>2</sub></small> formulation emerged as the most promising candidate, offering a strategic balance of mechanical integrity, bioactivity, and reproducibility. This optimized enzymatic system paves the way for scalable and clinically viable SF–G bioinks tailored for advanced tissue engineering and regenerative medicine applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7476-7498"},"PeriodicalIF":6.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuannan Chen, Jie Yu, Dongni Yao, Yangqi Zhao, Qiao Jin, Yao Liang, Yue Zhao, Yi Dong, Mengyue Xu, Peijin Qiu, Liqun Jin, Chaoyang Hong and Ting Shen
Ocular alkali burns are a severe ophthalmic emergency characterized by excessive production of reactive oxygen species (ROS), persistent inflammation, and corneal neovascularization, often resulting in visual impairment. We develop novel hybrid nanoparticles (CEL NPs) through coordination-driven self-assembly of Ce3+, ε-poly-L-lysine (EPL), and luteolin (Lut) to achieve synergistic ROS scavenging and anti-inflammatory effects. CEL NPs protect human corneal epithelial cells and macrophages from oxidative stress and apoptosis in vitro. CEL NPs also suppress inflammatory responses by inhibiting the NF-κB pathway while activating the Nrf2/HO-1 axis. They exhibit enhanced mucoadhesion and prolonged ocular retention in vivo. In a mouse model of alkali-induced corneal injury, topical CEL NPs markedly accelerate wound closure, reduce neovascularization, attenuate stromal edema, and decrease inflammatory cell infiltration. They outperform the individual components and match the efficacy of dexamethasone, without observable adverse effects. These results demonstrate a safe and effective nanotherapeutic strategy that combines dual redox modulation with anti-inflammatory mechanisms for treating ocular chemical injuries.
{"title":"Coordination-driven self-assembly of antioxidative and anti-inflammatory cerium–luteolin nanoparticles for effective treatment of ocular alkali burns","authors":"Chuannan Chen, Jie Yu, Dongni Yao, Yangqi Zhao, Qiao Jin, Yao Liang, Yue Zhao, Yi Dong, Mengyue Xu, Peijin Qiu, Liqun Jin, Chaoyang Hong and Ting Shen","doi":"10.1039/D6TB00573J","DOIUrl":"10.1039/D6TB00573J","url":null,"abstract":"<p >Ocular alkali burns are a severe ophthalmic emergency characterized by excessive production of reactive oxygen species (ROS), persistent inflammation, and corneal neovascularization, often resulting in visual impairment. We develop novel hybrid nanoparticles (CEL NPs) through coordination-driven self-assembly of Ce<small><sup>3+</sup></small>, ε-poly-<small>L</small>-lysine (EPL), and luteolin (Lut) to achieve synergistic ROS scavenging and anti-inflammatory effects. CEL NPs protect human corneal epithelial cells and macrophages from oxidative stress and apoptosis <em>in vitro</em>. CEL NPs also suppress inflammatory responses by inhibiting the NF-κB pathway while activating the Nrf2/HO-1 axis. They exhibit enhanced mucoadhesion and prolonged ocular retention <em>in vivo</em>. In a mouse model of alkali-induced corneal injury, topical CEL NPs markedly accelerate wound closure, reduce neovascularization, attenuate stromal edema, and decrease inflammatory cell infiltration. They outperform the individual components and match the efficacy of dexamethasone, without observable adverse effects. These results demonstrate a safe and effective nanotherapeutic strategy that combines dual redox modulation with anti-inflammatory mechanisms for treating ocular chemical injuries.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7719-7735"},"PeriodicalIF":6.2,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wang Zhang, Jingrou Sun, Ying Ou, Jing Zhang, Yilan Bai, Jingxi Hong, Lingchang Meng, Yi Song, Tiepeng Wang, Zhiting Sun and Jing Wu
Ulcerative colitis (UC) is a chronic inflammatory disorder of the intestine characterized by recurrent episodes. Current therapies exhibit limited efficacy and raise safety concerns. This study aimed to enhance the water solubility of the natural compound shikonin and improve its therapeutic efficacy by developing novel metal-phenolic nanoparticles. Zn-shikonin-PEG hybrid nanoparticles (Zn-SHK-PEG NPs) were synthesized by coordinating Zn2+ with shikonin and functionalizing the complex with polyethylene glycol (PEG). Dextran sulfate sodium (DSS)-induced colitis was employed to evaluate the therapeutic potential and mechanisms of the nanoparticles. Treatment with Zn-SHK-PEG NPs markedly alleviated weight loss and colon shortening, decreased the disease activity index (DAI), and reduced histopathological injury. Mechanistic investigations suggested that the nanoparticles reduced histidine decarboxylase (HDC) expression, which was associated with PKM2 regulation, accompanied by decreased histamine (HA) levels and suppressed inflammation. Furthermore, Zn-SHK-PEG NPs altered the gut microbiota composition, including enrichment of Akkermansia muciniphila, which may also contribute to the overall therapeutic effect. In summary, Zn-SHK-PEG NPs ameliorated DSS-induced colitis, and the therapeutic effects were associated with the regulation of the HDC/histamine axis, suppression of inflammatory responses, and modulation of gut microbiota. These findings suggest that Zn-SHK-PEG NPs may represent a potential strategy for ulcerative colitis treatment.
{"title":"A shikonin-based self-assembled nanomedicine alleviates DSS-induced colitis involving HDC-associated histamine regulation and gut microbiota modulation","authors":"Wang Zhang, Jingrou Sun, Ying Ou, Jing Zhang, Yilan Bai, Jingxi Hong, Lingchang Meng, Yi Song, Tiepeng Wang, Zhiting Sun and Jing Wu","doi":"10.1039/D6TB00517A","DOIUrl":"10.1039/D6TB00517A","url":null,"abstract":"<p >Ulcerative colitis (UC) is a chronic inflammatory disorder of the intestine characterized by recurrent episodes. Current therapies exhibit limited efficacy and raise safety concerns. This study aimed to enhance the water solubility of the natural compound shikonin and improve its therapeutic efficacy by developing novel metal-phenolic nanoparticles. Zn-shikonin-PEG hybrid nanoparticles (Zn-SHK-PEG NPs) were synthesized by coordinating Zn<small><sup>2+</sup></small> with shikonin and functionalizing the complex with polyethylene glycol (PEG). Dextran sulfate sodium (DSS)-induced colitis was employed to evaluate the therapeutic potential and mechanisms of the nanoparticles. Treatment with Zn-SHK-PEG NPs markedly alleviated weight loss and colon shortening, decreased the disease activity index (DAI), and reduced histopathological injury. Mechanistic investigations suggested that the nanoparticles reduced histidine decarboxylase (HDC) expression, which was associated with PKM2 regulation, accompanied by decreased histamine (HA) levels and suppressed inflammation. Furthermore, Zn-SHK-PEG NPs altered the gut microbiota composition, including enrichment of <em>Akkermansia muciniphila</em>, which may also contribute to the overall therapeutic effect. In summary, Zn-SHK-PEG NPs ameliorated DSS-induced colitis, and the therapeutic effects were associated with the regulation of the HDC/histamine axis, suppression of inflammatory responses, and modulation of gut microbiota. These findings suggest that Zn-SHK-PEG NPs may represent a potential strategy for ulcerative colitis treatment.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7659-7675"},"PeriodicalIF":6.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/tb/d6tb00517a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junjie Zou, Lijuan Yang, Wenxiang Zhang, Gang Liu and Zhixiang Lu
Conventional optical imaging is constrained by photon absorption and multiple scattering in biological tissues. Extending excitation and emission into the second near-infrared window (NIR-II, 1000–1700 nm) markedly suppresses tissue autofluorescence and improves imaging fidelity. However, enhanced optical performance alone does not ensure clinical translatability. In this review, we distinguish the conceptual boundary between optical probes and translational optical agents, highlighting the critical role of formulation engineering in bridging material functionality with biomedical applicability. Representative NIR-II probe classes are summarized together with their intrinsic advantages and translational limitations. We further discuss key formulation strategies for optical agent construction, including targeting engineering, hydrophilicity regulation, size optimization, and carrier-assisted integration. Recent advances in cardiovascular, oncological, neurological, and multimodal imaging applications are also reviewed. Finally, remaining challenges related to biosafety, imaging hardware, and clinical standardization are discussed. By adopting a formulation-centered perspective, this review emphasizes the transition from signal-generating probes to clinically relevant optical agents and outlines future directions for accelerating the translation of NIR-II imaging toward precision diagnostics and image-guided medicine.
{"title":"From materials to medicine: formulation-driven optimization and clinical prospects of NIR-II optical imaging agents","authors":"Junjie Zou, Lijuan Yang, Wenxiang Zhang, Gang Liu and Zhixiang Lu","doi":"10.1039/D6TB00661B","DOIUrl":"10.1039/D6TB00661B","url":null,"abstract":"<p >Conventional optical imaging is constrained by photon absorption and multiple scattering in biological tissues. Extending excitation and emission into the second near-infrared window (NIR-II, 1000–1700 nm) markedly suppresses tissue autofluorescence and improves imaging fidelity. However, enhanced optical performance alone does not ensure clinical translatability. In this review, we distinguish the conceptual boundary between optical probes and translational optical agents, highlighting the critical role of formulation engineering in bridging material functionality with biomedical applicability. Representative NIR-II probe classes are summarized together with their intrinsic advantages and translational limitations. We further discuss key formulation strategies for optical agent construction, including targeting engineering, hydrophilicity regulation, size optimization, and carrier-assisted integration. Recent advances in cardiovascular, oncological, neurological, and multimodal imaging applications are also reviewed. Finally, remaining challenges related to biosafety, imaging hardware, and clinical standardization are discussed. By adopting a formulation-centered perspective, this review emphasizes the transition from signal-generating probes to clinically relevant optical agents and outlines future directions for accelerating the translation of NIR-II imaging toward precision diagnostics and image-guided medicine.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7412-7434"},"PeriodicalIF":6.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/tb/d6tb00661b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Ma, Minghao Zhou, Juan Tong, Bin Zhu, Jin Liu, Hongbo Wei, Kun Xuan, Xinyu Qiu and Jiang Wang
Wound healing still faces many significant challenges, such as excessive oxidative stress, persistent inflammation and disrupted angiogenesis. To overcome these obstacles, we developed a biomimetic hybrid regulatory platform (ApoEVs@FeSe2–RGD) by anchoring redox-active FeSe2 nanorods onto mesenchymal stem cell-derived apoptotic extracellular vesicles (ApoEVs), followed by surface functionalization with cyclic RGD (cRGD) peptides. This regulator effectively synergizes the robust reactive oxygen species (ROS)-scavenging capacity of FeSe2 with the exceptional biocompatibility of cRGD-functionalized ApoEVs. In vitro assessments revealed that ApoEVs@FeSe2–RGD efficiently cleared abnormally produced ROS to recalibrate the oxidative microenvironment. Consequently, it inhibited pro-inflammatory activation while driving macrophage polarization toward an anti-inflammatory phenotype. The reparative cytokines derived from these reprogrammed macrophages significantly enhanced the migration, proliferation, and angiogenic capacity of endothelial cells. Furthermore, the in vivo assessments in a full-thickness wound healing model demonstrated that this vesicle-scaffolded regulator enhanced the wound closure rate and promoted re-epithelialization, collagen deposition, and neovascularization with good biosafety. Mechanistically, transcriptomic profiling combined with protein validation demonstrated that these therapeutic effects were mediated by the suppression of the NF-κB signaling pathway. Collectively, our study demonstrated that ApoEVs@FeSe2–RGD holds potential as a therapeutic strategy for wound healing by restoring redox homeostasis and orchestrating immune–vascularization coupling for high-quality tissue regeneration.
{"title":"ApoEVs@FeSe2–RGD as a synergistic redox–immune regulator for accelerating wound healing","authors":"Zhen Ma, Minghao Zhou, Juan Tong, Bin Zhu, Jin Liu, Hongbo Wei, Kun Xuan, Xinyu Qiu and Jiang Wang","doi":"10.1039/D6TB00418K","DOIUrl":"10.1039/D6TB00418K","url":null,"abstract":"<p >Wound healing still faces many significant challenges, such as excessive oxidative stress, persistent inflammation and disrupted angiogenesis. To overcome these obstacles, we developed a biomimetic hybrid regulatory platform (ApoEVs@FeSe<small><sub>2</sub></small>–RGD) by anchoring redox-active FeSe<small><sub>2</sub></small> nanorods onto mesenchymal stem cell-derived apoptotic extracellular vesicles (ApoEVs), followed by surface functionalization with cyclic RGD (cRGD) peptides. This regulator effectively synergizes the robust reactive oxygen species (ROS)-scavenging capacity of FeSe<small><sub>2</sub></small> with the exceptional biocompatibility of cRGD-functionalized ApoEVs. <em>In vitro</em> assessments revealed that ApoEVs@FeSe<small><sub>2</sub></small>–RGD efficiently cleared abnormally produced ROS to recalibrate the oxidative microenvironment. Consequently, it inhibited pro-inflammatory activation while driving macrophage polarization toward an anti-inflammatory phenotype. The reparative cytokines derived from these reprogrammed macrophages significantly enhanced the migration, proliferation, and angiogenic capacity of endothelial cells. Furthermore, the <em>in vivo</em> assessments in a full-thickness wound healing model demonstrated that this vesicle-scaffolded regulator enhanced the wound closure rate and promoted re-epithelialization, collagen deposition, and neovascularization with good biosafety. Mechanistically, transcriptomic profiling combined with protein validation demonstrated that these therapeutic effects were mediated by the suppression of the NF-κB signaling pathway. Collectively, our study demonstrated that ApoEVs@FeSe<small><sub>2</sub></small>–RGD holds potential as a therapeutic strategy for wound healing by restoring redox homeostasis and orchestrating immune–vascularization coupling for high-quality tissue regeneration.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7688-7705"},"PeriodicalIF":6.2,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengqin Zhang, Yang Wu, Ling Hu, Dongni Pei, Jianxiu Wang and Xinyao Yi
The development of intelligent nanoplatforms that integrate tumor targeting, stimuli-responsive drug release, and multimodal therapy remains a significant challenge for precise cancer treatment. Herein, a nanoplatform based on DNA nanoflowers and Mn:CuS nanoparticles with a unique architecture and multiple therapeutic functions was constructed. The DNA nanoflowers derived from rolling circle amplification (RCA) served as the scaffold, enabling the efficient intercalation of Mn:CuS nanoparticles and doxorubicin (DOX). Furthermore, the sgc-8 aptamer was incorporated into the DNA scaffold for specific recognition of HeLa cells. The intercalated Mn:CuS nanoparticles exhibited photothermal therapeutic activity, peroxidase (POD)/oxidase (OXD)-like properties and glutathione peroxidase (GPx)-like activity, thus achieving amplified therapeutic efficacy toward tumor cells. Moreover, the DOX release was demonstrated to be precisely controllable in acidic environments and under near-infrared (NIR) irradiation, which ensured tumor-specific drug release. Thus, synergistic chemotherapy, photothermal therapy and chemo-dynamic therapy (CDT) of cancers were achieved. Compared with the conventional single-function nanocarriers, this multifunctional hybrid system combines specific target recognition, responsive drug delivery, and multimodal therapeutic treatment, offering a promising avenue for precise and effective cancer therapy.
{"title":"An intelligent responsive nanoplatform based on a DNA nanoflowers/Mn:CuS hybrid for targeted and synergistic cancer therapy","authors":"Mengqin Zhang, Yang Wu, Ling Hu, Dongni Pei, Jianxiu Wang and Xinyao Yi","doi":"10.1039/D5TB02930A","DOIUrl":"10.1039/D5TB02930A","url":null,"abstract":"<p >The development of intelligent nanoplatforms that integrate tumor targeting, stimuli-responsive drug release, and multimodal therapy remains a significant challenge for precise cancer treatment. Herein, a nanoplatform based on DNA nanoflowers and Mn:CuS nanoparticles with a unique architecture and multiple therapeutic functions was constructed. The DNA nanoflowers derived from rolling circle amplification (RCA) served as the scaffold, enabling the efficient intercalation of Mn:CuS nanoparticles and doxorubicin (DOX). Furthermore, the sgc-8 aptamer was incorporated into the DNA scaffold for specific recognition of HeLa cells. The intercalated Mn:CuS nanoparticles exhibited photothermal therapeutic activity, peroxidase (POD)/oxidase (OXD)-like properties and glutathione peroxidase (GPx)-like activity, thus achieving amplified therapeutic efficacy toward tumor cells. Moreover, the DOX release was demonstrated to be precisely controllable in acidic environments and under near-infrared (NIR) irradiation, which ensured tumor-specific drug release. Thus, synergistic chemotherapy, photothermal therapy and chemo-dynamic therapy (CDT) of cancers were achieved. Compared with the conventional single-function nanocarriers, this multifunctional hybrid system combines specific target recognition, responsive drug delivery, and multimodal therapeutic treatment, offering a promising avenue for precise and effective cancer therapy.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7604-7614"},"PeriodicalIF":6.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Outer membrane vesicles (OMVs), naturally released by Gram-negative bacteria, represent a unique class of bionanomaterials with inherent immunogenicity, efficient cellular delivery, and scalable production. However, their native toxicity, compositional heterogeneity, and lack of targeting specificity have hindered broader therapeutic translation. Advances in genetic engineering and synthetic biology have revolutionized OMV design, transforming these biological byproducts into highly programmable bionanomaterial platforms. This review systematically outlines the key engineering strategies for OMVs, including surface display for targeting and immunomodulation, cargo loading for encapsulating nucleic acids, proteins, and drugs, and membrane modulation for tuning stability and safety. We highlight the transformative applications of genetically engineered OMVs (geOMVs) in cancer immunotherapy, next-generation vaccines, targeted delivery, and diagnostic imaging. Finally, we discuss the critical challenges in the clinical translation—such as scalable manufacturing, safety profiling, and regulatory pathways—and propose future directions integrating synthetic biology, materials science, and artificial intelligence to realize the full potential of geOMVs as intelligent, precision therapeutic and diagnostic platforms.
{"title":"Genetically engineered outer membrane vesicles as next-generation bionanomaterials for therapeutic and diagnostic applications","authors":"Xuyu Bian, Ziyan Huang, Chenhang Xu, Jiawei Yue and Yumin Wu","doi":"10.1039/D6TB00650G","DOIUrl":"10.1039/D6TB00650G","url":null,"abstract":"<p >Outer membrane vesicles (OMVs), naturally released by Gram-negative bacteria, represent a unique class of bionanomaterials with inherent immunogenicity, efficient cellular delivery, and scalable production. However, their native toxicity, compositional heterogeneity, and lack of targeting specificity have hindered broader therapeutic translation. Advances in genetic engineering and synthetic biology have revolutionized OMV design, transforming these biological byproducts into highly programmable bionanomaterial platforms. This review systematically outlines the key engineering strategies for OMVs, including surface display for targeting and immunomodulation, cargo loading for encapsulating nucleic acids, proteins, and drugs, and membrane modulation for tuning stability and safety. We highlight the transformative applications of genetically engineered OMVs (geOMVs) in cancer immunotherapy, next-generation vaccines, targeted delivery, and diagnostic imaging. Finally, we discuss the critical challenges in the clinical translation—such as scalable manufacturing, safety profiling, and regulatory pathways—and propose future directions integrating synthetic biology, materials science, and artificial intelligence to realize the full potential of geOMVs as intelligent, precision therapeutic and diagnostic platforms.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7400-7411"},"PeriodicalIF":6.2,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kallol Roy, Esha Roy, Nibedita Saikia, Pankaj Barman, Binoy K. Saikia and Rituraj Konwar
Infectious diseases are a major global health issue despite the development of antibiotics and chemotherapy. There is an unmet need for the development of novel therapeutic and diagnostic agents to combat emerging and multi-drug-resistant microorganisms. To overcome these issues, carbon-based quantum dots (QDs), i.e., carbon quantum dots (CQDs) and graphene quantum dots (GQDs), can be an alternative approach due to their diverse and distinct properties, such as chemical inertness, low toxicity, biocompatibility, and photostability. Engineered QDs (EQDs) prepared by integrating various moieties through doping, functionalization, surface passivation, or combination with antimicrobial substances have vast biological applications in the management of infectious diseases. The current review aims to comprehensively discuss the recent progress on pharmacological mechanisms and detection strategies of native QDs (CQDs and GQDs), and EQDs against a wide range of infectious disease-causing pathogens, namely, bacteria, viruses, fungi, and parasites. The major mechanisms of their action involve cell wall/membrane disruption, replication and transcription inhibition, excessive ROS generation, immune response pathway activation, and synergistic interactions with antimicrobial agents. In addition, EQDs integrated diverse detection strategies, including optical, nucleic acid, immune, lateral flow assay, electrochemistry, emphasizing their potential use as sensitive probes for the rapid monitoring of pathogens in biological and environmental samples. Finally, the evolving scenarios of regulatory requirements, potential toxicity, and challenges in their clinical translation are addressed in this review. The current review will certainly be useful in advancing research activities for developing new affordable antimicrobial drugs and diagnostic agents using native QDs/EQDs.
{"title":"Engineered carbon-based quantum dots: a next-generation nanomedicine for the therapy and diagnosis of infectious diseases","authors":"Kallol Roy, Esha Roy, Nibedita Saikia, Pankaj Barman, Binoy K. Saikia and Rituraj Konwar","doi":"10.1039/D5TB02755A","DOIUrl":"10.1039/D5TB02755A","url":null,"abstract":"<p >Infectious diseases are a major global health issue despite the development of antibiotics and chemotherapy. There is an unmet need for the development of novel therapeutic and diagnostic agents to combat emerging and multi-drug-resistant microorganisms. To overcome these issues, carbon-based quantum dots (QDs), <em>i.e.</em>, carbon quantum dots (CQDs) and graphene quantum dots (GQDs), can be an alternative approach due to their diverse and distinct properties, such as chemical inertness, low toxicity, biocompatibility, and photostability. Engineered QDs (EQDs) prepared by integrating various moieties through doping, functionalization, surface passivation, or combination with antimicrobial substances have vast biological applications in the management of infectious diseases. The current review aims to comprehensively discuss the recent progress on pharmacological mechanisms and detection strategies of native QDs (CQDs and GQDs), and EQDs against a wide range of infectious disease-causing pathogens, namely, bacteria, viruses, fungi, and parasites. The major mechanisms of their action involve cell wall/membrane disruption, replication and transcription inhibition, excessive ROS generation, immune response pathway activation, and synergistic interactions with antimicrobial agents. In addition, EQDs integrated diverse detection strategies, including optical, nucleic acid, immune, lateral flow assay, electrochemistry, emphasizing their potential use as sensitive probes for the rapid monitoring of pathogens in biological and environmental samples. Finally, the evolving scenarios of regulatory requirements, potential toxicity, and challenges in their clinical translation are addressed in this review. The current review will certainly be useful in advancing research activities for developing new affordable antimicrobial drugs and diagnostic agents using native QDs/EQDs.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 24","pages":" 7435-7475"},"PeriodicalIF":6.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyu Ma, Zhuang Zhang, Dandan Yang, Hui Wang, Hao Zhang, Yue Yang, Siying Li and Yuping Shan
Beyond the canonical angiotensin-converting enzyme 2 (ACE2)-mediated entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells, basigin (BSG) and dipeptidyl peptidase 4 (DPP4) may also act as alternative receptors that can facilitate viral attachment and subsequent endocytosis. Herein, we analyzed the binding efficiency and binding dynamics of SARS-CoV-2 virus-like particles (VLPs), mediated by BSG and DPP4 at the single-particle level, by combining super-resolution direct stochastic optical reconstruction microscopy (dSTORM) and single-molecule force spectroscopy (SMFS). dSTORM imaging demonstrated that DPP4 exhibits higher surface expression levels than BSG on HepG2 cells. However, SARS-CoV-2 VLPs display a distinct preference for BSG-dependent cellular entry. Using SMFS, we further probed the binding dynamics between the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and these two receptors. The results demonstrated that RBD-BSG exhibits greater stability and a more rapid formation rate compared to RBD-DPP4. Subsequently, a real-time force tracing technique was used to show that BSG-mediated VLP entry requires lower force and faster speed compared with DPP4-mediated entry. In particular, we confirmed that the structural integrity of intramolecular disulfide bonds within the RBD is indispensable for mediating high-affinity receptor binding. These findings elucidate the distinct receptor-mediated endocytic dynamic mechanisms underlying SARS-CoV-2 entry mediated by BSG and DPP4, expanding our understanding of viral invasion beyond the ACE2 pathway and providing insights into potential intervention strategies targeting viral infection.
除了典型的血管紧张素转换酶2 (ACE2)介导的严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)进入宿主细胞外,basigin (BSG)和二肽基肽酶4 (DPP4)也可能作为替代受体,促进病毒附着和随后的内吞作用。本研究采用超分辨率直接随机光学重建显微镜(dSTORM)和单分子力谱(SMFS)技术,在单粒子水平上分析了BSG和DPP4介导的SARS-CoV-2病毒样颗粒(VLPs)的结合效率和结合动力学。dSTORM成像显示,DPP4在HepG2细胞上的表面表达水平高于BSG。然而,SARS-CoV-2 VLPs明显倾向于依赖bsg的细胞进入。利用SMFS,我们进一步探讨了SARS-CoV-2刺突蛋白受体结合域(spike - S protein receptor-binding domain, RBD)与这两种受体的结合动力学。结果表明,与RBD-DPP4相比,RBD-BSG具有更高的稳定性和更快的形成速度。随后,采用实时力追踪技术显示,与dpp4介导的进入相比,bsg介导的VLP进入所需的力更小,速度更快。特别是,我们证实了RBD分子内二硫键的结构完整性对于介导高亲和力受体结合是必不可少的。这些发现阐明了BSG和DPP4介导的SARS-CoV-2进入的独特受体介导的内吞动力学机制,扩展了我们对ACE2途径之外的病毒入侵的理解,并为针对病毒感染的潜在干预策略提供了见解。
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Hunter B. Wood, Joseph T. Dosch, Stella M. Trickett, Juhi Singh, Farin M. Weinger, Gerald J. Wang, Dazhe J. Cao and Stefanie A. Sydlik
Drug overdose remains a major public health challenge, particularly for non-opioid substances that lack effective antidotes and are often treated through gastrointestinal decontamination with activated charcoal. While activated charcoal is broadly effective, its use is associated with aspiration risks and gastrointestinal complications. Here, we report a class of synthetic poly(glutamic acid-block-tyrosine) (EY) peptide adsorbent materials designed as biocompatible, tuneable alternatives for gastrointestinal drug adsorption. EY polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization with systematically varied tyrosine block lengths to investigate how amino acid composition and length govern adsorption. Adsorption kinetics and capacity were evaluated under simulated gastric (pH 1.2) and intestinal (pH 6.8) conditions for clinically relevant drugs commonly implicated in overdose: amitriptyline (AMI), bupropion (BUP), hydroxychloroquine (HCQ), and strychnine (STR). Increasing tyrosine content enhanced drug uptake, with the top-performing formulation (E30Y129) achieving high adsorption capacities and binding affinities comparable to reported adsorbent biopolymers and competitive with activated charcoal for certain drugs. Langmuir isotherm analysis revealed maximum adsorption capacities of 40–238 mg g−1 and binding affinities up to 0.214 L g−1, with adsorption behavior dependent on drug characteristics. Exploratory fed-state experiments demonstrated that adsorbent properties are retained in the presence of a complex nutrient matrix and vary depending on drug properties. Preliminary enzyme degradation studies indicated gradual proteolysis under gastrointestinal conditions, and cytocompatibility assays with fibroblasts and macrophages showed no overt toxicity across relevant concentrations. Collectively, these results demonstrate that synthetic polypeptides can be engineered to achieve efficient, clinically relevant drug adsorption while offering advantages in biocompatibility, degradability, and tunability. This work establishes a foundation for next-generation gastrointestinal decontamination materials beyond activated charcoal.
药物过量仍然是一个重大的公共卫生挑战,特别是对于缺乏有效解毒剂的非阿片类物质,通常通过活性炭对胃肠道进行净化来治疗。虽然活性炭广泛有效,但其使用与误吸风险和胃肠道并发症有关。在这里,我们报道了一类合成的聚谷氨酸块酪氨酸(EY)肽吸附材料,设计为生物相容性,可调节的胃肠道药物吸附替代品。采用n -羧基氢化开环聚合法制备不同酪氨酸嵌段长度的EY多肽,研究氨基酸组成和长度对吸附的影响。在模拟胃(pH 1.2)和肠道(pH 6.8)条件下,对阿米替林(AMI)、安非他酮(BUP)、羟氯喹(HCQ)和士的宁(STR)等临床相关药物的吸附动力学和容量进行了评估。酪氨酸含量的增加增强了药物的吸收,性能最好的配方(E30Y129)具有高吸附能力和结合亲和力,与报道的吸附剂生物聚合物相当,在某些药物上与活性炭竞争。Langmuir等温线分析表明,吸附量为40 ~ 238 mg g-1,结合亲和度为0.214 L g-1,吸附行为与药物特性有关。探索性实验表明,吸附剂的性质在复杂的营养基质中保持不变,并根据药物性质而变化。初步的酶降解研究表明,在胃肠道条件下,蛋白质会逐渐分解,成纤维细胞和巨噬细胞的细胞相容性实验显示,在相关浓度下,没有明显的毒性。总的来说,这些结果表明,合成多肽可以在生物相容性、可降解性和可调性方面具有优势的同时,实现有效的、临床相关的药物吸附。本研究为开发活性炭以外的下一代胃肠道净化材料奠定了基础。
{"title":"Poly(glutamic acid-block-tyrosine) peptides designed for gastrointestinal drug adsorption","authors":"Hunter B. Wood, Joseph T. Dosch, Stella M. Trickett, Juhi Singh, Farin M. Weinger, Gerald J. Wang, Dazhe J. Cao and Stefanie A. Sydlik","doi":"10.1039/D6TB00121A","DOIUrl":"10.1039/D6TB00121A","url":null,"abstract":"<p >Drug overdose remains a major public health challenge, particularly for non-opioid substances that lack effective antidotes and are often treated through gastrointestinal decontamination with activated charcoal. While activated charcoal is broadly effective, its use is associated with aspiration risks and gastrointestinal complications. Here, we report a class of synthetic poly(glutamic acid-<em>block</em>-tyrosine) (EY) peptide adsorbent materials designed as biocompatible, tuneable alternatives for gastrointestinal drug adsorption. EY polypeptides were synthesized <em>via N</em>-carboxyanhydride ring-opening polymerization with systematically varied tyrosine block lengths to investigate how amino acid composition and length govern adsorption. Adsorption kinetics and capacity were evaluated under simulated gastric (pH 1.2) and intestinal (pH 6.8) conditions for clinically relevant drugs commonly implicated in overdose: amitriptyline (AMI), bupropion (BUP), hydroxychloroquine (HCQ), and strychnine (STR). Increasing tyrosine content enhanced drug uptake, with the top-performing formulation (E30Y129) achieving high adsorption capacities and binding affinities comparable to reported adsorbent biopolymers and competitive with activated charcoal for certain drugs. Langmuir isotherm analysis revealed maximum adsorption capacities of 40–238 mg g<small><sup>−1</sup></small> and binding affinities up to 0.214 L g<small><sup>−1</sup></small>, with adsorption behavior dependent on drug characteristics. Exploratory fed-state experiments demonstrated that adsorbent properties are retained in the presence of a complex nutrient matrix and vary depending on drug properties. Preliminary enzyme degradation studies indicated gradual proteolysis under gastrointestinal conditions, and cytocompatibility assays with fibroblasts and macrophages showed no overt toxicity across relevant concentrations. Collectively, these results demonstrate that synthetic polypeptides can be engineered to achieve efficient, clinically relevant drug adsorption while offering advantages in biocompatibility, degradability, and tunability. This work establishes a foundation for next-generation gastrointestinal decontamination materials beyond activated charcoal.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 23","pages":" 7280-7297"},"PeriodicalIF":6.2,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/tb/d6tb00121a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}