Pub Date : 2026-01-12DOI: 10.1021/acs.biomac.5c01204
Taylor M. Page , Kai Ludwig , Muhammad Shayan Haider , Elisa Quaas , Alexandros Mavroskoufis , Peng Tang , Rui Chen , Jun Feng, Raju Bej , Katharina Achazi , Rainer Haag , Ievgen S. Donskyi
Targeted drug delivery systems that are stimuli-responsive offer great potential for enhancing the therapeutic activity of drugs, decreasing off-target effects, and improving bioavailability. This proof-of-concept study introduces an amphiphilic drug delivery system (DDS) capable of loading hydrophobic cargo. Elevated glutathione (GSH) levels, characteristic of certain types of cancer cells’ microenvironment, degrade the nanostructures and release the cargo. Linear polyglycerol sulfate (LPGS), known for its excellent biocompatibility, is combined with lipoic acid (LA). LA facilitates the formation of cross-linked nanosheet amphiphiles sensitive to reductive conditions. Morphological changes are observed by scanning electron microscopy (SEM), cryogenic transmission electron microscopy (Cryo-TEM), and cryogenic electron tomography (Cryo-ET) upon UV irradiation (hν), creating a stable aggregate for loading hydrophobic cargo and assembling into sheets at elevated concentrations. The resulting material displays controlled release of model dyes under increased levels of GSH, tunable by the polymer size and LPGS:LA acid ratios. This behavior enhances targeted therapy and reduced off-target effects. Further loading with paclitaxel and subsequent release, together with in vitro assays, demonstrates the system’s compatibility with an anticancer drug.
{"title":"Redox-Responsive Self-Assembled Amphiphilic Nanosheets from Polyglycerol Sulfate–Lipoic Acid Copolymers for Targeted Cancer Drug Delivery","authors":"Taylor M. Page , Kai Ludwig , Muhammad Shayan Haider , Elisa Quaas , Alexandros Mavroskoufis , Peng Tang , Rui Chen , Jun Feng, Raju Bej , Katharina Achazi , Rainer Haag , Ievgen S. Donskyi","doi":"10.1021/acs.biomac.5c01204","DOIUrl":"10.1021/acs.biomac.5c01204","url":null,"abstract":"<div><div>Targeted drug delivery systems that are stimuli-responsive offer great potential for enhancing the therapeutic activity of drugs, decreasing off-target effects, and improving bioavailability. This proof-of-concept study introduces an amphiphilic drug delivery system (DDS) capable of loading hydrophobic cargo. Elevated glutathione (GSH) levels, characteristic of certain types of cancer cells’ microenvironment, degrade the nanostructures and release the cargo. Linear polyglycerol sulfate (LPGS), known for its excellent biocompatibility, is combined with lipoic acid (LA). LA facilitates the formation of cross-linked nanosheet amphiphiles sensitive to reductive conditions. Morphological changes are observed by scanning electron microscopy (SEM), cryogenic transmission electron microscopy (Cryo-TEM), and cryogenic electron tomography (Cryo-ET) upon UV irradiation (<em>h</em>ν), creating a stable aggregate for loading hydrophobic cargo and assembling into sheets at elevated concentrations. The resulting material displays controlled release of model dyes under increased levels of GSH, tunable by the polymer size and LPGS:LA acid ratios. This behavior enhances targeted therapy and reduced off-target effects. Further loading with paclitaxel and subsequent release, together with <em>in vitro</em> assays, demonstrates the system’s compatibility with an anticancer drug.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 249-258"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659837","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c02091
Sarah G. Fisher, Zachary Buck, Margaret J. Karim, Jaime C. Grunlan
Food packaging is critical to prevent food waste, but most of the packaging used today is not sustainable. Paper-based packaging materials offer a renewable option, but exhibit poor resistance to common permeants such as oxygen, grease, and water vapor. In this work, a complex coacervate coating is prepared from two waste biopolymers, gelatin and DNA, and applied to kraft paper to substantially improve its barrier properties. Thermally curing the coating after deposition decreases the water vapor transmission rate and oxygen transmission rate by 83 and 99%, respectively, relative to uncoated paper. This work represents one of the best fully biobased barrier coatings reported for paper and is a promising option for sustainable food packaging.
{"title":"Fish-Based Biopolymer Complex Coacervate Coating for Improved Paper Oxygen and Water Barrier","authors":"Sarah G. Fisher, Zachary Buck, Margaret J. Karim, Jaime C. Grunlan","doi":"10.1021/acs.biomac.5c02091","DOIUrl":"10.1021/acs.biomac.5c02091","url":null,"abstract":"<div><div>Food packaging is critical to prevent food waste, but most of the packaging used today is not sustainable. Paper-based packaging materials offer a renewable option, but exhibit poor resistance to common permeants such as oxygen, grease, and water vapor. In this work, a complex coacervate coating is prepared from two waste biopolymers, gelatin and DNA, and applied to kraft paper to substantially improve its barrier properties. Thermally curing the coating after deposition decreases the water vapor transmission rate and oxygen transmission rate by 83 and 99%, respectively, relative to uncoated paper. This work represents one of the best fully biobased barrier coatings reported for paper and is a promising option for sustainable food packaging.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 795-804"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601293","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c01601
Zhichun Lin, Yizhen Yan , Archie Hunter, Huaiyu Yang
Understanding protein–salt interactions is important for controlling crystallization, including biomineralization, biopharmaceutical purification, biocatalytic enzymes, and environmental biointerfaces. This study for the first time investigated interactions between three proteins (lysozyme, red fluorescence protein, and bovine hemoglobin) and Li2CO3 (formation from the reaction of LiCl with Na2CO3) under different protein and salt concentrations. For the crystallization of Li2CO3, at low supersaturation (S), the proteins inhibited Li2CO3 nucleation by 20–40% through chelation. At high S, the proteins accelerated nucleation by 10–40%. The dual effects of the protein on Li2CO3 biomineralization have been discussed. With the increase S of Li2CO3, the dispersion state of proteins in solution undergoes a transition from dimers to oligomers and finally to aggregates. In all ranges of S, the protein reduced the agglomeration of Li2CO3 crystals. In lysozyme crystallization, increasing the Li2CO3 concentration yielded a larger number of smaller crystals. At equal concentration of lysozyme, twice more of LiCl and Na2CO3 in the solution led to more than 5 times the crystal number and 5 times smaller average crystal size. The interactions among protein molecules, salt ions in solution, and Li2CO3 crystals have been discussed. Dynamic light scattering measurements and the fluorescence microscopy image suggest that the dual effect of proteins on Li2CO3 crystallization at different supersaturation levels is associated with protein molecular aggregation under varying salt concentrations, resulting in both thermodynamic and kinetic influences on the crystallization process.
{"title":"Protein Self-Assembly States Modulate Lithium Carbonate Biomineralization: From Ion Chelation to Nucleation Sites","authors":"Zhichun Lin, Yizhen Yan , Archie Hunter, Huaiyu Yang","doi":"10.1021/acs.biomac.5c01601","DOIUrl":"10.1021/acs.biomac.5c01601","url":null,"abstract":"<div><div>Understanding protein–salt interactions is important for controlling crystallization, including biomineralization, biopharmaceutical purification, biocatalytic enzymes, and environmental biointerfaces. This study for the first time investigated interactions between three proteins (lysozyme, red fluorescence protein, and bovine hemoglobin) and Li<sub>2</sub>CO<sub>3</sub> (formation from the reaction of LiCl with Na<sub>2</sub>CO<sub>3</sub>) under different protein and salt concentrations. For the crystallization of Li<sub>2</sub>CO<sub>3</sub>, at low supersaturation (<em>S</em>), the proteins inhibited Li<sub>2</sub>CO<sub>3</sub> nucleation by 20–40% through chelation. At high <em>S</em>, the proteins accelerated nucleation by 10–40%. The dual effects of the protein on Li<sub>2</sub>CO<sub>3</sub> biomineralization have been discussed. With the increase <em>S</em> of Li<sub>2</sub>CO<sub>3</sub>, the dispersion state of proteins in solution undergoes a transition from dimers to oligomers and finally to aggregates. In all ranges of <em>S</em>, the protein reduced the agglomeration of Li<sub>2</sub>CO<sub>3</sub> crystals. In lysozyme crystallization, increasing the Li<sub>2</sub>CO<sub>3</sub> concentration yielded a larger number of smaller crystals. At equal concentration of lysozyme, twice more of LiCl and Na<sub>2</sub>CO<sub>3</sub> in the solution led to more than 5 times the crystal number and 5 times smaller average crystal size. The interactions among protein molecules, salt ions in solution, and Li<sub>2</sub>CO<sub>3</sub> crystals have been discussed. Dynamic light scattering measurements and the fluorescence microscopy image suggest that the dual effect of proteins on Li<sub>2</sub>CO<sub>3</sub> crystallization at different supersaturation levels is associated with protein molecular aggregation under varying salt concentrations, resulting in both thermodynamic and kinetic influences on the crystallization process.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 428-438"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740111","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c02107
Wenyu Zhu , Yiying Ye , Li Zhang , Guangyao Zhao , Jianbo Tan
Polymeric microspheres are indispensable in catalysis, coatings, and biomedical analysis, yet conventional dispersion polymerization requires high stabilizer loadings and often yields surfaces with limited functional accessibility. Here, we report a molecular bottlebrush strategy that overcomes these limitations by employing reversible addition–fragmentation chain transfer (RAFT)-derived macromonomers, followed by ring-opening metathesis polymerization (ROMP) to generate bottlebrush stabilizers for photoinitiated RAFT dispersion polymerization. These bottlebrushes afford robust steric stabilization at significantly reduced loadings and enrich microsphere surfaces with RAFT end groups, enabling facile postpolymerization modification. The resulting PMMA microspheres exhibit exceptional monodispersity, tunable diameters, and versatile surface functionality. Subsequent photoiniferter polymerization yields carboxyl-functionalized microspheres with grafted poly(acrylic acid) chains, providing a high density of accessible carboxyl groups for biomacromolecule conjugation. Optimization of the chain length reveals a critical balance between loading capacity and accessibility, leading to markedly improved performance in bead-based immunoassays. This bottlebrush-mediated approach thus establishes a general and scalable platform for producing size-controlled, surface-functional polymeric microspheres with enhanced bioanalytical utility.
{"title":"Molecular Bottlebrush-Stabilized Polymeric Microspheres by Photoinitiated RAFT Dispersion Polymerization for Bead-Based Immunoassays","authors":"Wenyu Zhu , Yiying Ye , Li Zhang , Guangyao Zhao , Jianbo Tan","doi":"10.1021/acs.biomac.5c02107","DOIUrl":"10.1021/acs.biomac.5c02107","url":null,"abstract":"<div><div>Polymeric microspheres are indispensable in catalysis, coatings, and biomedical analysis, yet conventional dispersion polymerization requires high stabilizer loadings and often yields surfaces with limited functional accessibility. Here, we report a molecular bottlebrush strategy that overcomes these limitations by employing reversible addition–fragmentation chain transfer (RAFT)-derived macromonomers, followed by ring-opening metathesis polymerization (ROMP) to generate bottlebrush stabilizers for photoinitiated RAFT dispersion polymerization. These bottlebrushes afford robust steric stabilization at significantly reduced loadings and enrich microsphere surfaces with RAFT end groups, enabling facile postpolymerization modification. The resulting PMMA microspheres exhibit exceptional monodispersity, tunable diameters, and versatile surface functionality. Subsequent photoiniferter polymerization yields carboxyl-functionalized microspheres with grafted poly(acrylic acid) chains, providing a high density of accessible carboxyl groups for biomacromolecule conjugation. Optimization of the chain length reveals a critical balance between loading capacity and accessibility, leading to markedly improved performance in bead-based immunoassays. This bottlebrush-mediated approach thus establishes a general and scalable platform for producing size-controlled, surface-functional polymeric microspheres with enhanced bioanalytical utility.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 822-834"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699226","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}
Geckos adhere reliably to vertical and inverted surfaces, making them an appealing model for biomimetic adhesives. Yet a complete understanding of how this adhesion works remains elusive, primarily because the underlying mechanisms span multiple length scales. We used a hybrid particle-continuum model to simulate a gecko seta during pull-off tests. We examined how dragging the seta laterally on the substrate, varying drag distance and direction (distal or proximal), and the seta stalk angle influence the pull-off force. Across all conditions, increasing the drag distance raised the pull-off force. This resulted from a reduced peel-off angle before detachment, not from a larger contact area. Higher stalk angles (62° and 72°) also increased adhesion via a lower peel-off angle. Furthermore, distal dragging yielded up to 50% greater pull-off forces than proximal dragging, revealing anisotropic, directionally controllable adhesion. These results clarify how adhesion is tuned and suggest principles for bioinspired, direction-switchable adhesives.
{"title":"Angle- and Lateral Drag-Dependent Pull-Off Behavior of a Single Gecko Spatula: Insights from a Concurrent Molecular-Continuum Model","authors":"Saeed Norouzi , Tobias Materzok , Stanislav Gorb , Florian Müller-Plathe","doi":"10.1021/acs.biomac.5c01991","DOIUrl":"10.1021/acs.biomac.5c01991","url":null,"abstract":"<div><div>Geckos adhere reliably to vertical and inverted surfaces, making them an appealing model for biomimetic adhesives. Yet a complete understanding of how this adhesion works remains elusive, primarily because the underlying mechanisms span multiple length scales. We used a hybrid particle-continuum model to simulate a gecko seta during pull-off tests. We examined how dragging the seta laterally on the substrate, varying drag distance and direction (distal or proximal), and the seta stalk angle influence the pull-off force. Across all conditions, increasing the drag distance raised the pull-off force. This resulted from a reduced peel-off angle before detachment, not from a larger contact area. Higher stalk angles (62° and 72°) also increased adhesion via a lower peel-off angle. Furthermore, distal dragging yielded up to 50% greater pull-off forces than proximal dragging, revealing anisotropic, directionally controllable adhesion. These results clarify how adhesion is tuned and suggest principles for bioinspired, direction-switchable adhesives.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 733-746"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699308","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c02040
Yajing Liu , Bo Zou , Zhenhao Teng , Litao Wang , Ning Zhang , Na Zhao , Xiaofeng Wang , Qian Li , Xiaomeng Li
Rapid hemorrhage control and effective tissue regeneration are essential for improving outcomes in trauma and surgical wound management. Adhesive hydrogels adapt to irregular wounds but lack sufficient interconnected macroporosity for effective cell infiltration and tissue remodeling. Herein, a macroporous silk fibroin methacryloyl (SilMA) hydrospongel was developed via a simple foaming strategy. The foamed hydrospongel exhibits gel-like behavior before cross-linking and can be further stabilized through in situ photo-cross-linking. The SilMA hydrospongel achieves rapid hemostasis by absorbing blood and enhancing platelet aggregation and clot formation. Beyond hemostatic performance, its interconnected porous structure facilitates cellular infiltration and supports tissue integration, while its conformability and adhesion ensure seamless conformity to irregular wounds. Furthermore, the hydrospongel reduces fibrosis and scar formation in cutaneous and cardiac wounds by modulating the immune microenvironment. Collectively, this study demonstrates the translational potential of the hydrospongel as a multifunctional system for hemostasis, tissue regeneration, and drug delivery.
{"title":"Silk Fibroin Hydrospongel with Interconnected Porosity and Robust Adhesion for Rapid Hemostasis and Scarless Repair","authors":"Yajing Liu , Bo Zou , Zhenhao Teng , Litao Wang , Ning Zhang , Na Zhao , Xiaofeng Wang , Qian Li , Xiaomeng Li","doi":"10.1021/acs.biomac.5c02040","DOIUrl":"10.1021/acs.biomac.5c02040","url":null,"abstract":"<div><div>Rapid hemorrhage control and effective tissue regeneration are essential for improving outcomes in trauma and surgical wound management. Adhesive hydrogels adapt to irregular wounds but lack sufficient interconnected macroporosity for effective cell infiltration and tissue remodeling. Herein, a macroporous silk fibroin methacryloyl (SilMA) hydrospongel was developed <em>via</em> a simple foaming strategy. The foamed hydrospongel exhibits gel-like behavior before cross-linking and can be further stabilized through in situ photo-cross-linking. The SilMA hydrospongel achieves rapid hemostasis by absorbing blood and enhancing platelet aggregation and clot formation. Beyond hemostatic performance, its interconnected porous structure facilitates cellular infiltration and supports tissue integration, while its conformability and adhesion ensure seamless conformity to irregular wounds. Furthermore, the hydrospongel reduces fibrosis and scar formation in cutaneous and cardiac wounds by modulating the immune microenvironment. Collectively, this study demonstrates the translational potential of the hydrospongel as a multifunctional system for hemostasis, tissue regeneration, and drug delivery.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 764-782"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861290","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c02147
Yi-Bo Yuan, Miao-Miao Yin, Zhi-Yu Zuo, Na Zhang, He-Chang Huang, Meng-Kang Jiang, Xin Ding, Yan-Jun Hu
Metal–organic frameworks’ (MOFs) biomedical performance is largely determined by surface ligands and the “protein corona” that forms in biological environments. Corona composition critically influences MOF behavior, yet how ligands direct corona formation and subsequent structure-protein-cell cascades remains poorly understood. Here, using MIL-101(Fe) as a model, three functionalized derivatives (H-, NH2-, NO2-MIL-101(Fe)) were constructed via electron-donating and electron-withdrawing groups. Ligand electronic effects critically modulate binding to serum proteins (HSA and transferrin), yielding distinct affinities (H ≥ NH2 > NO2) and interaction mechanisms (hydrogen bonding vs electrostatic). Cellular studies revealed that HSA coronas enhance the biocompatibility of MOFs in normal hepatocytes, while TRF coronas promote uptake, reactive oxygen species generation, and mitochondrial damage in 4T1 cancer cells, thereby amplifying cytotoxicity. This work systematically elucidates how ligand functionalization orchestrates protein corona structure and the subsequent protein-cell cascade, providing a mechanistic basis and design strategy for precise biomedical applications of MOFs.
{"title":"Ligand-Mediated Protein Corona on MIL-101(Fe) Governs Cytotoxicity via a Structure-Protein-Cell Cascade","authors":"Yi-Bo Yuan, Miao-Miao Yin, Zhi-Yu Zuo, Na Zhang, He-Chang Huang, Meng-Kang Jiang, Xin Ding, Yan-Jun Hu","doi":"10.1021/acs.biomac.5c02147","DOIUrl":"10.1021/acs.biomac.5c02147","url":null,"abstract":"<div><div>Metal–organic frameworks’ (MOFs) biomedical performance is largely determined by surface ligands and the “protein corona” that forms in biological environments. Corona composition critically influences MOF behavior, yet how ligands direct corona formation and subsequent structure-protein-cell cascades remains poorly understood. Here, using MIL-101(Fe) as a model, three functionalized derivatives (H-, NH<sub>2</sub>-, NO<sub>2</sub>-MIL-101(Fe)) were constructed via electron-donating and electron-withdrawing groups. Ligand electronic effects critically modulate binding to serum proteins (HSA and transferrin), yielding distinct affinities (H ≥ NH<sub>2</sub> > NO<sub>2</sub>) and interaction mechanisms (hydrogen bonding vs electrostatic). Cellular studies revealed that HSA coronas enhance the biocompatibility of MOFs in normal hepatocytes, while TRF coronas promote uptake, reactive oxygen species generation, and mitochondrial damage in 4T1 cancer cells, thereby amplifying cytotoxicity. This work systematically elucidates how ligand functionalization orchestrates protein corona structure and the subsequent protein-cell cascade, providing a mechanistic basis and design strategy for precise biomedical applications of MOFs.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 873-886"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831851","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c01648
Chenikkayala Siva Sankara , Akanksha Ramadas Shanbhag , Daniel Rincón Díaz , Caitlyn A. Hodges , Chenglong Li , Jeffrey K. Harrison , Fan Zhang
Small-molecule STAT3 inhibitors face numerous challenges in clinical translation, including poor water solubility, rapid systemic clearance, low bioavailability, poor selectivity, and high cytotoxicity. To address these limitations, we conjugated the potent STAT3 inhibitor–LLL12 to generate six (G6) hydroxyl-terminated (poly(amidoamine)) PAMAM dendrimers using pH-sensitive linkers: sulfonyl carbamate (carbamate), sulfonyl carbamoyl (amide), and hydrazone for intracellular drug delivery. Conjugation greatly enhanced LLL12 solubility (up to 10 mg/mL) and reduced cytotoxicity without altering dendrimer size or surface charge. All three G6-LLL12 conjugates remained stable under neutral pH but exhibited sustained, pH-dependent drug release correlating with in vitro potency and cytotoxicity. Notably, hydrazone-linked conjugate showed an IC50 = 0.42 ± 0.035 μg/mL, comparable to free LLL12 (IC50 = 0.31 ± 0.05 μg/mL) and superior to amide- and carbamate-linked conjugates. In bone marrow-derived immune suppressive myeloid cells, hydrazone-based G6-LLL12 effectively reduciii-derrive, hydrazone-based G6-LLL12 effectively reduced monocytic myeloid-derived suppressor cell expansion and promoted antigen-presenting cell maturation, highlighting a promising pH-responsive delivery system that enhances solubility and safety while retaining potency.
{"title":"Engineering pH-Responsive Dendrimer–STAT3 Inhibitor Conjugates for Intracellular Delivery","authors":"Chenikkayala Siva Sankara , Akanksha Ramadas Shanbhag , Daniel Rincón Díaz , Caitlyn A. Hodges , Chenglong Li , Jeffrey K. Harrison , Fan Zhang","doi":"10.1021/acs.biomac.5c01648","DOIUrl":"10.1021/acs.biomac.5c01648","url":null,"abstract":"<div><div>Small-molecule STAT3 inhibitors face numerous challenges in clinical translation, including poor water solubility, rapid systemic clearance, low bioavailability, poor selectivity, and high cytotoxicity. To address these limitations, we conjugated the potent STAT3 inhibitor–LLL12 to generate six (G6) hydroxyl-terminated (poly(amidoamine)) PAMAM dendrimers using pH-sensitive linkers: sulfonyl carbamate (carbamate), sulfonyl carbamoyl (amide), and hydrazone for intracellular drug delivery. Conjugation greatly enhanced LLL12 solubility (up to 10 mg/mL) and reduced cytotoxicity without altering dendrimer size or surface charge. All three G6-LLL12 conjugates remained stable under neutral pH but exhibited sustained, pH-dependent drug release correlating with <em>in vitro</em> potency and cytotoxicity. Notably, hydrazone-linked conjugate showed an IC<sub>50</sub> = 0.42 ± 0.035 μg/mL, comparable to free LLL12 (IC<sub>50</sub> = 0.31 ± 0.05 μg/mL) and superior to amide- and carbamate-linked conjugates. In bone marrow-derived immune suppressive myeloid cells, hydrazone-based G6-LLL12 effectively reduciii-derrive, hydrazone-based G6-LLL12 effectively reduced monocytic myeloid-derived suppressor cell expansion and promoted antigen-presenting cell maturation, highlighting a promising pH-responsive delivery system that enhances solubility and safety while retaining potency.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 459-474"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626897","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c01718
Wei-Qi Lu , Ming-Min Zhou , Jin-Qiang Peng , Xiao-Yun Han , Jian-Ling Mo , Jian Ji , Ke-Feng Ren , Xia Sheng
Postoperative atrial fibrillation (POAF) is a common surgical complication linked to atrial inflammation and oxidative stress. Here, we developed a strategy integrating chemical modification of therapeutics, poly(lactic-co-glycolic acid) (PLGA)-mediated sustained kinetics, and hydrogel-enabled spatial targeting to achieve continuous, local drug delivery to the atrial region. Andrographolide was modified with phenylboronic acid (PBAn) to change its solubility and enhance drug-loading capacity in PLGA microspheres, while enabling responsive drug release. We further constructed an injectable bioadhesive hydrogel via mixing of a copolymer and O-carboxymethyl chitosan, which adhered to cardiac tissue. In vitro, PBAn demonstrated ROS-responsive release, along with anti-inflammatory and antioxidant effects on RAW264.7 and HL-1 cells. In a rat pericarditis model, this localized system significantly reduced atrial inflammation and oxidative stress, promoted anti-inflammatory M2 macrophage polarization, enhanced electrical stability, and markedly decreased POAF susceptibility.
{"title":"An Anti-Inflammatory and Antioxidant Patch Based on Injectable Bioadhesive Hydrogel Prevents Postoperative Atrial Fibrillation","authors":"Wei-Qi Lu , Ming-Min Zhou , Jin-Qiang Peng , Xiao-Yun Han , Jian-Ling Mo , Jian Ji , Ke-Feng Ren , Xia Sheng","doi":"10.1021/acs.biomac.5c01718","DOIUrl":"10.1021/acs.biomac.5c01718","url":null,"abstract":"<div><div>Postoperative atrial fibrillation (POAF) is a common surgical complication linked to atrial inflammation and oxidative stress. Here, we developed a strategy integrating chemical modification of therapeutics, poly(lactic-<em>co</em>-glycolic acid) (PLGA)-mediated sustained kinetics, and hydrogel-enabled spatial targeting to achieve continuous, local drug delivery to the atrial region. Andrographolide was modified with phenylboronic acid (PBAn) to change its solubility and enhance drug-loading capacity in PLGA microspheres, while enabling responsive drug release. We further constructed an injectable bioadhesive hydrogel via mixing of a copolymer and O-carboxymethyl chitosan, which adhered to cardiac tissue. In vitro, PBAn demonstrated ROS-responsive release, along with anti-inflammatory and antioxidant effects on RAW264.7 and HL-1 cells. In a rat pericarditis model, this localized system significantly reduced atrial inflammation and oxidative stress, promoted anti-inflammatory M2 macrophage polarization, enhanced electrical stability, and markedly decreased POAF susceptibility.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 492-506"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626966","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 : 2026-01-12DOI: 10.1021/acs.biomac.5c00986
Xianheng Wang , Jie Fang , Lei Yang , Weijie Liu , Li Xiao , Yiwen Li
Reactive oxygen species (ROS) are vital but harmful in excess, and numerous small molecule antioxidants (e.g., polyphenols) can help to maintain an optimal ROS balance. Considering factors like biocompatibility, it is more commonly preferred to transform these natural antioxidants into nanoscavengers through a macromolecular engineering strategy. However, conventional macromolecular antioxidants typically exhibit decreased scavenging capacity compared to monomers due to steric hindrance and oxidation during the polymerization. To tackle this issue, we developed robust degradable macromolecular nanoscavengers by polymerizing dopamine and 4-formylphenylboronic acid. Featuring boronate–catechol linkages, these nanoscavengers boost antioxidation by degrading and exposing functional groups in acidic or ROS environments, showing greater capacity than monomers and polydopamine nanoparticles. Those nanoscavengers were subsequently employed to temporomandibular joint osteoarthritis, suppressing both oxidative stress and inflammation to effectively alleviate the disease progression. This study offers new insights into the design and synthesis of degradable macromolecular antioxidants for inflammation treatment.
{"title":"A Degradable Macromolecular Antioxidant for Efficient Arthritis Treatment","authors":"Xianheng Wang , Jie Fang , Lei Yang , Weijie Liu , Li Xiao , Yiwen Li","doi":"10.1021/acs.biomac.5c00986","DOIUrl":"10.1021/acs.biomac.5c00986","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) are vital but harmful in excess, and numerous small molecule antioxidants (e.g., polyphenols) can help to maintain an optimal ROS balance. Considering factors like biocompatibility, it is more commonly preferred to transform these natural antioxidants into nanoscavengers through a macromolecular engineering strategy. However, conventional macromolecular antioxidants typically exhibit decreased scavenging capacity compared to monomers due to steric hindrance and oxidation during the polymerization. To tackle this issue, we developed robust degradable macromolecular nanoscavengers by polymerizing dopamine and 4-formylphenylboronic acid. Featuring boronate–catechol linkages, these nanoscavengers boost antioxidation by degrading and exposing functional groups in acidic or ROS environments, showing greater capacity than monomers and polydopamine nanoparticles. Those nanoscavengers were subsequently employed to temporomandibular joint osteoarthritis, suppressing both oxidative stress and inflammation to effectively alleviate the disease progression. This study offers new insights into the design and synthesis of degradable macromolecular antioxidants for inflammation treatment.</div></div><div><div><span><figure></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 1","pages":"Pages 164-178"},"PeriodicalIF":5.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626910","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}