Pub Date : 2026-03-09Epub Date: 2026-02-25DOI: 10.1021/acs.biomac.6c00036
Jing Guo , Kun Luo , Xin-Yu Dai , Yao Li , Teng Fu , Lei-Xiao Yu , Ke-Ke Yang
Osteoarthritis (OA) is the most common degenerative joint disease, which is largely driven by the deterioration of cartilage lubrication. However, current lubricants, such as hyaluronic acid (HA), suffer from poor mechanical resilience and rapid enzymatic degradation. Herein, we develop a structurally engineered lubricant, HPG-g-pSBMA (HgS), constructed by grafting zwitterionic poly(sulfobetaine methacrylate) (pSBMA) chains onto a globular hyperbranched polyglycerol (HPG) core. The hyperbranched topology minimizes molecular entanglement and shear thinning, while the dense zwitterionic shell forms a robust hydration layer that resists compression and frictional wear. HgS exhibits superior lubrication efficacy at a low concentration (1 mg/mL) with enhanced injectability, significantly outperforming 10 mg/mL HA. Molecular simulations reveal strong hydration shell formation and hydration-mediated disruption of solute–solute interactions. HgS demonstrates excellent biocompatibility and enzymatic stability, prolonged intra-articular retention, and effective inhibition of OA progression in vivo. This work highlights a topology-guided design strategy for durable and efficient joint lubricants for OA treatment.
{"title":"Topology-Engineered Hyperbranched Zwitterionic Polymer Enabling Robust Hydration Lubrication in Osteoarthritic Joints","authors":"Jing Guo , Kun Luo , Xin-Yu Dai , Yao Li , Teng Fu , Lei-Xiao Yu , Ke-Ke Yang","doi":"10.1021/acs.biomac.6c00036","DOIUrl":"10.1021/acs.biomac.6c00036","url":null,"abstract":"<div><div>Osteoarthritis (OA) is the most common degenerative joint disease, which is largely driven by the deterioration of cartilage lubrication. However, current lubricants, such as hyaluronic acid (HA), suffer from poor mechanical resilience and rapid enzymatic degradation. Herein, we develop a structurally engineered lubricant, HPG-<em>g</em>-pSBMA (HgS), constructed by grafting zwitterionic poly(sulfobetaine methacrylate) (pSBMA) chains onto a globular hyperbranched polyglycerol (HPG) core. The hyperbranched topology minimizes molecular entanglement and shear thinning, while the dense zwitterionic shell forms a robust hydration layer that resists compression and frictional wear. HgS exhibits superior lubrication efficacy at a low concentration (1 mg/mL) with enhanced injectability, significantly outperforming 10 mg/mL HA. Molecular simulations reveal strong hydration shell formation and hydration-mediated disruption of solute–solute interactions. HgS demonstrates excellent biocompatibility and enzymatic stability, prolonged intra-articular retention, and effective inhibition of OA progression <em>in vivo</em>. This work highlights a topology-guided design strategy for durable and efficient joint lubricants for OA treatment.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (361KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 2352-2365"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281086","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 : 2026-03-09Epub Date: 2025-09-16DOI: 10.1021/acs.biomac.5c01404
Yuan J. Hou , Rui M. Guo , Fang Li , De S. Fan , Cheng Z. Xu , Lian Zhu , Jun T. Zhang , Ben M. Wei , Hai B. Wang
The cooperative interplay between type I collagen (COL) and fibronectin (FN) in the extracellular matrix (ECM) guides both matrix organization and cell behavior. While COL-based materials are widely used, their limited capacity to integrate FN-mediated regulatory cues restricts functional biomimicry. Here, we investigate how COL/FN composites in distinct assembly states (monomeric vs fibrillar) differentially regulate cellular responses. Biophysical characterization confirmed FN binding to COL α chains promotes coassembly into hybrid fibrils with accelerated kinetics and enhanced mechanical rigidity. Strikingly, HT1080 cells exhibited opposing adhesion behaviors on monomeric versus fibrillar COL/FN matrices. In monomeric matrices, escalating FN ratios progressively reduced adhesion, while in fibrillar matrices, low-FN ratios enhanced adhesion synergistically. Cell migration followed an inverse pattern, with monomeric hybrids promoting motility and fibrillar matrices suppressing it. Our findings highlight that COL/FN assembly states, independent of compositional changes, dictate cell–matrix reciprocity through structural reconfiguration. This work establishes a paradigm for engineering ECM-inspired materials with phase-specific topographies to guide cellular decision-making, advancing applications in tissue regeneration and mechanobiology studies.
{"title":"Collagen-Fibronectin Crosstalk in Engineered Matrices: Synergistic Assembly Orchestrates Fibrillar Morphogenesis and Cell Adhesion-Migration Dynamics","authors":"Yuan J. Hou , Rui M. Guo , Fang Li , De S. Fan , Cheng Z. Xu , Lian Zhu , Jun T. Zhang , Ben M. Wei , Hai B. Wang","doi":"10.1021/acs.biomac.5c01404","DOIUrl":"10.1021/acs.biomac.5c01404","url":null,"abstract":"<div><div>The cooperative interplay between type I collagen (COL) and fibronectin (FN) in the extracellular matrix (ECM) guides both matrix organization and cell behavior. While COL-based materials are widely used, their limited capacity to integrate FN-mediated regulatory cues restricts functional biomimicry. Here, we investigate how COL/FN composites in distinct assembly states (monomeric vs fibrillar) differentially regulate cellular responses. Biophysical characterization confirmed FN binding to COL α chains promotes coassembly into hybrid fibrils with accelerated kinetics and enhanced mechanical rigidity. Strikingly, HT1080 cells exhibited opposing adhesion behaviors on monomeric versus fibrillar COL/FN matrices. In monomeric matrices, escalating FN ratios progressively reduced adhesion, while in fibrillar matrices, low-FN ratios enhanced adhesion synergistically. Cell migration followed an inverse pattern, with monomeric hybrids promoting motility and fibrillar matrices suppressing it. Our findings highlight that COL/FN assembly states, independent of compositional changes, dictate cell–matrix reciprocity through structural reconfiguration. This work establishes a paradigm for engineering ECM-inspired materials with phase-specific topographies to guide cellular decision-making, advancing applications in tissue regeneration and mechanobiology studies.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (259KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 1819-1830"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068657","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}
According to the requirements of modern society for durable biomaterials with multiple functionalities, the principal target of this study was to apply the “grafting to” scheme on the synthesis of several hybrid copolymers based on amylopectin (AMP) and poly(N-isopropylacrylamide) (PNIPAM), poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) as synthetic polymer components, thus obtaining hybrid copolymers responsive to different stimuli, such as temperature, pH, and ionic strength. The synthetic polymers were synthesized by reversible addition–fragmentation chain transfer polymerization and contain reactive carboxyl groups attached to one end of the polymeric chains. The successful synthesis of novel graft copolymers AMP-g-PNIPAM, AMP-g-PDMAEMA, and AMP-g-POEGMA was confirmed by ATR-FTIR and 1H NMR spectroscopies, by evidencing the appearance of new aliphatic ether bonds as a consequence of covalent grafting of the synthetic polymers onto the AMP chains. The pH, temperature, and ionic strength responsiveness of the newly obtained copolymers’ aqueous solutions were followed by dynamic and electrophoretic light scattering analysis, revealing the intra/interchain self-assembly depending on the ionizable groups present in their structure, according to their protonation or deprotonation equilibria.
{"title":"Amylopectin Copolymers Grafted with RAFT-Obtained Synthetic Polymers: Synthesis and Aqueous Solution Behavior","authors":"Melinda-Maria Bazarghideanu, Marius-Mihai Zaharia, Ana-Maria Macsim, Marcela Mihai, Stergios Pispas","doi":"10.1021/acs.biomac.5c02198","DOIUrl":"10.1021/acs.biomac.5c02198","url":null,"abstract":"<div><div>According to the requirements of modern society for durable biomaterials with multiple functionalities, the principal target of this study was to apply the “grafting to” scheme on the synthesis of several hybrid copolymers based on amylopectin (AMP) and poly(<em>N</em>-isopropylacrylamide) (PNIPAM), poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) as synthetic polymer components, thus obtaining hybrid copolymers responsive to different stimuli, such as temperature, pH, and ionic strength. The synthetic polymers were synthesized by reversible addition–fragmentation chain transfer polymerization and contain reactive carboxyl groups attached to one end of the polymeric chains. The successful synthesis of novel graft copolymers AMP-<em>g</em>-PNIPAM, AMP-<em>g</em>-PDMAEMA, and AMP-<em>g</em>-POEGMA was confirmed by ATR-FTIR and <sup>1</sup>H NMR spectroscopies, by evidencing the appearance of new aliphatic ether bonds as a consequence of covalent grafting of the synthetic polymers onto the AMP chains. The pH, temperature, and ionic strength responsiveness of the newly obtained copolymers’ aqueous solutions were followed by dynamic and electrophoretic light scattering analysis, revealing the intra/interchain self-assembly depending on the ionizable groups present in their structure, according to their protonation or deprotonation equilibria.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (65KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 1985-1998"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155375","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 : 2026-03-09Epub Date: 2026-02-10DOI: 10.1021/acs.biomac.5c02390
Mengyuan Cao , François Fay , Adrouchan Hotier , Séverine Domenichini , Lucile Alexandre , Christopher Ribes , Florence Gazeau , Hervé Hillaireau , Elias Fattal
Activated proinflammatory macrophages are associated with various inflammatory diseases, and due to their overexpression of the CD44 receptor, they may be targeted for therapy by hyaluronic acid (HA), its natural ligand. This study aimed to develop lipid nanoparticles (LNPs) functionalized with HA and stabilized with an optimized amount of poly(ethylene glycol) (PEG) for targeted mRNA delivery to activated macrophages. Using microfluidic mixing, LNPs were produced with either 1.5% PEG (LNP1.5%PEG) or 0.5% PEG (LNP0.5%PEG). HA-coated LNPs (HA-LNPs) were prepared by postinsertion of an HA–DPPE conjugate, and changes in size and zeta potential demonstrated a successful and efficient HA coating, which was quantified by spectrofluorimetry and nanoscale flow cytometry. In vitro studies showed that HA-LNP0.5%PEG exhibited better uptake in activated macrophages while maintaining mRNA transfection efficiency, whereas HA-LNP1.5%PEG did not improve its uptake, suggesting that excessive PEG can hinder targeting. Overall, HA-LNP0.5%PEG effectively delivered mRNA to activated macrophages with enhanced selectivity.
{"title":"Selective mRNA Delivery to Activated Macrophages via Hyaluronic Acid-Functionalized Lipid Nanoparticles with Optimized PEGylation","authors":"Mengyuan Cao , François Fay , Adrouchan Hotier , Séverine Domenichini , Lucile Alexandre , Christopher Ribes , Florence Gazeau , Hervé Hillaireau , Elias Fattal","doi":"10.1021/acs.biomac.5c02390","DOIUrl":"10.1021/acs.biomac.5c02390","url":null,"abstract":"<div><div>Activated proinflammatory macrophages are associated with various inflammatory diseases, and due to their overexpression of the CD44 receptor, they may be targeted for therapy by hyaluronic acid (HA), its natural ligand. This study aimed to develop lipid nanoparticles (LNPs) functionalized with HA and stabilized with an optimized amount of poly(ethylene glycol) (PEG) for targeted mRNA delivery to activated macrophages. Using microfluidic mixing, LNPs were produced with either 1.5% PEG (LNP<sub>1.5%PEG</sub>) or 0.5% PEG (LNP<sub>0.5%PEG</sub>). HA-coated LNPs (HA-LNPs) were prepared by postinsertion of an HA–DPPE conjugate, and changes in size and zeta potential demonstrated a successful and efficient HA coating, which was quantified by spectrofluorimetry and nanoscale flow cytometry. In vitro studies showed that HA-LNP<sub>0.5%PEG</sub> exhibited better uptake in activated macrophages while maintaining mRNA transfection efficiency, whereas HA-LNP<sub>1.5%PEG</sub> did not improve its uptake, suggesting that excessive PEG can hinder targeting. Overall, HA-LNP<sub>0.5%PEG</sub> effectively delivered mRNA to activated macrophages with enhanced selectivity.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (82KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 2078-2090"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155364","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 : 2026-03-09Epub Date: 2026-02-12DOI: 10.1021/acs.biomac.5c01949
Fei Fu , Aiping Yu , Mingming Yu , Fuhao Dong , Shanshan Wang , Li Wang , Xu Xu , He Liu
Conventional monofilament sutures often exhibit limited mechanical performance, such as insufficient flexibility and ligation strength, which can lead to tissue cutting or damage during surgical procedures. To address these limitations, the fabrication of polyurethane monofilament sutures by combining multiblock polymers (polydimethylsiloxane (PDMS)/polycaprolactone (PCL)) and a hierarchical hydrogen-bonding network is reported. Hierarchical hydrogen bonds and microphase separation in the material together form dynamic hard-phase microdomains, which act as rigid nanofillers that deform and reorganize under external forces. Consequently, the suture demonstrates outstanding mechanical properties, including a true stress of 393 MPa, an elongation at break of 610%, and an ultrahigh toughness of 941 MJ m–3, surpassing commercial nylon, silk, and other reported suture materials. Furthermore, cytotoxicity tests and mouse tests confirm excellent biocompatibility and effective wound healing. Overall, this polyurethane suture overcomes the key mechanical limitations of traditional monofilament sutures and shows strong potential for surgical applications.
{"title":"Innovative Fabrication of Monofilament Sutures with High Strength, Resilience, and Ultratoughness for Enhanced Wound Healing","authors":"Fei Fu , Aiping Yu , Mingming Yu , Fuhao Dong , Shanshan Wang , Li Wang , Xu Xu , He Liu","doi":"10.1021/acs.biomac.5c01949","DOIUrl":"10.1021/acs.biomac.5c01949","url":null,"abstract":"<div><div>Conventional monofilament sutures often exhibit limited mechanical performance, such as insufficient flexibility and ligation strength, which can lead to tissue cutting or damage during surgical procedures. To address these limitations, the fabrication of polyurethane monofilament sutures by combining multiblock polymers (polydimethylsiloxane (PDMS)/polycaprolactone (PCL)) and a hierarchical hydrogen-bonding network is reported. Hierarchical hydrogen bonds and microphase separation in the material together form dynamic hard-phase microdomains, which act as rigid nanofillers that deform and reorganize under external forces. Consequently, the suture demonstrates outstanding mechanical properties, including a true stress of 393 MPa, an elongation at break of 610%, and an ultrahigh toughness of 941 MJ m<sup>–3</sup>, surpassing commercial nylon, silk, and other reported suture materials. Furthermore, cytotoxicity tests and mouse tests confirm excellent biocompatibility and effective wound healing. Overall, this polyurethane suture overcomes the key mechanical limitations of traditional monofilament sutures and shows strong potential for surgical applications.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (83KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 1867-1877"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177089","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 : 2026-03-09Epub Date: 2026-02-12DOI: 10.1021/acs.biomac.5c02023
Yoshinori Doi , Kazuho Daicho , Ryosuke Kusumi , Jun Ashida , Antonie Gorissen , Ries de Visser , Shuji Fujisawa , Tsuguyuki Saito
The crystallinity of cellulose decreases as the cell wall structure of pulp fibrillates to cellulose nanofibers (CNFs) in water. The decreased crystallinity is partially recovered when the CNFs are reassembled into bulk structures through dehydration. We analyzed the molecular mechanism that underlies these changes in crystallinity via two-dimensional 13C–13C solid-state nuclear magnetic resonance (NMR) spectroscopy. A cellulose sample was extracted from a 13C-labeled Norway spruce (Picea abies) and then subjected to 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidation. This oxidation aims to regioselectively convert the C6 hydroxymethyl groups exposed on microfibril surfaces to carboxylate groups, which enables these oxidized glucuronate residues to function as surface markers. The C4 carbons within the oxidized residues remained noncrystalline through both fibrillation and reassembly. Other internal carbons of nonoxidized glucose residues underwent reversible and coordinated transitions between the crystalline and noncrystalline states, accounting for the changes in crystallinity detected via NMR. The presence of two surface environments, i.e., interfibril interfaces and air-exposed surfaces, was also suggested.
{"title":"Molecular Mechanism Underlying the Crystallinity Changes of Cellulose upon Fibrillation and Reassembly Revealed via Two-Dimensional Solid-State NMR","authors":"Yoshinori Doi , Kazuho Daicho , Ryosuke Kusumi , Jun Ashida , Antonie Gorissen , Ries de Visser , Shuji Fujisawa , Tsuguyuki Saito","doi":"10.1021/acs.biomac.5c02023","DOIUrl":"10.1021/acs.biomac.5c02023","url":null,"abstract":"<div><div>The crystallinity of cellulose decreases as the cell wall structure of pulp fibrillates to cellulose nanofibers (CNFs) in water. The decreased crystallinity is partially recovered when the CNFs are reassembled into bulk structures through dehydration. We analyzed the molecular mechanism that underlies these changes in crystallinity via two-dimensional <sup>13</sup>C–<sup>13</sup>C solid-state nuclear magnetic resonance (NMR) spectroscopy. A cellulose sample was extracted from a <sup>13</sup>C-labeled Norway spruce (<em>Picea abies</em>) and then subjected to 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidation. This oxidation aims to regioselectively convert the C6 hydroxymethyl groups exposed on microfibril surfaces to carboxylate groups, which enables these oxidized glucuronate residues to function as surface markers. The C4 carbons within the oxidized residues remained noncrystalline through both fibrillation and reassembly. Other internal carbons of nonoxidized glucose residues underwent reversible and coordinated transitions between the crystalline and noncrystalline states, accounting for the changes in crystallinity detected via NMR. The presence of two surface environments, i.e., interfibril interfaces and air-exposed surfaces, was also suggested.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (69KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 1905-1914"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177073","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 : 2026-03-09Epub Date: 2026-02-17DOI: 10.1021/acs.biomac.5c02567
Avijit Ghosh, Mansi Sharma, Yan Zhao
Overexpressed ATP-binding cassette (ABC) transporters, such as multidrug resistance protein 1 (MRP1) encoded by ABCC1, are responsible for multidrug resistance in anticancer treatment due to their abilities to prevent drugs from reaching their lethal intracellular concentrations. Similar overexpression of drug efflux pumps is a major contributor to antimicrobial resistance seen in bacteria. We report sequence-selective, molecularly imprinted nanoparticles (MINPs) targeting MRP1 in human cancer cells. These nanoparticles mask different segments of the long, flexible linker connecting NBD1 (nucleotide-binding domain 1) and TMD2 (transmembrane domain 2) of MRP1. Binding of the protein near the inner membrane interface is found to strongly inhibit the function of the efflux pump and sensitize Dox-resistant cancer cells to the drug, reducing its IC50 value by ∼25%. These results illustrate a new strategy for inhibiting intracellular proteins and identifying potential functional linear motifs in unstructured regions of proteins, benefiting from the facile preparation of the MINPs for different peptide sequences, their highly specific binding abilities, and their ability to enter cells.
{"title":"Reining in Multidrug Resistance Protein 1 via Binding Its Flexible Interdomain Linker with Sequence-Selective Peptide-Binding Nanoparticles","authors":"Avijit Ghosh, Mansi Sharma, Yan Zhao","doi":"10.1021/acs.biomac.5c02567","DOIUrl":"10.1021/acs.biomac.5c02567","url":null,"abstract":"<div><div>Overexpressed ATP-binding cassette (ABC) transporters, such as multidrug resistance protein 1 (MRP1) encoded by ABCC1, are responsible for multidrug resistance in anticancer treatment due to their abilities to prevent drugs from reaching their lethal intracellular concentrations. Similar overexpression of drug efflux pumps is a major contributor to antimicrobial resistance seen in bacteria. We report sequence-selective, molecularly imprinted nanoparticles (MINPs) targeting MRP1 in human cancer cells. These nanoparticles mask different segments of the long, flexible linker connecting NBD1 (nucleotide-binding domain 1) and TMD2 (transmembrane domain 2) of MRP1. Binding of the protein near the inner membrane interface is found to strongly inhibit the function of the efflux pump and sensitize Dox-resistant cancer cells to the drug, reducing its IC<sub>50</sub> value by ∼25%. These results illustrate a new strategy for inhibiting intracellular proteins and identifying potential functional linear motifs in unstructured regions of proteins, benefiting from the facile preparation of the MINPs for different peptide sequences, their highly specific binding abilities, and their ability to enter cells.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (95KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 2223-2233"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206109","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 : 2026-03-09Epub Date: 2026-02-19DOI: 10.1021/acs.biomac.5c02529
M. Klein , L. Alambik , C. Le Coz , T. Tassaing , I. Fabre-Francke , T. Vidil , H. Cramail
We report the original synthesis of two abietic acid derivatives, epoxidized maleopimarate oleylamide (EMPOA) and epoxidized maleopimarate undecenamide (EMPUA), which uniquely combine epoxy and anhydride functions within a single molecular structure. Their ability to undergo self-polymerization was first investigated, and fully cross-linked thermosets were subsequently obtained by copolymerizing EMPOA and EMPUA with a series of commercial biobased epoxides derived from vanillin, glycerol, and vegetable oils. A key advantage of EMPOA lies in its excellent miscibility with epoxidized vegetable oils, providing low-viscosity mixtures that can be readily blended with other epoxy resins without requiring large amounts of solvent. Epoxidized soybean oil (ESBO) proved to be an efficient reactive diluent, reducing solvent use to trace levels. Cross-linked materials with glassy-state moduli in the gigapascal range, comparable to fossil-based thermosets, were obtained. These results establish EMPOA and EMPUA as promising dual-reactive monomers for the design of high-performance and fully biobased thermosetting materials.
{"title":"Abietic Acid Derivatives Combining Epoxy and Anhydride Functionalities: Self- and Co-Polymerization toward Fully Bio-Based Thermosets","authors":"M. Klein , L. Alambik , C. Le Coz , T. Tassaing , I. Fabre-Francke , T. Vidil , H. Cramail","doi":"10.1021/acs.biomac.5c02529","DOIUrl":"10.1021/acs.biomac.5c02529","url":null,"abstract":"<div><div>We report the original synthesis of two abietic acid derivatives, epoxidized maleopimarate oleylamide (<strong>EMPOA</strong>) and epoxidized maleopimarate undecenamide (<strong>EMPUA</strong>), which uniquely combine epoxy and anhydride functions within a single molecular structure. Their ability to undergo self-polymerization was first investigated, and fully cross-linked thermosets were subsequently obtained by copolymerizing <strong>EMPOA</strong> and <strong>EMPUA</strong> with a series of commercial biobased epoxides derived from vanillin, glycerol, and vegetable oils. A key advantage of <strong>EMPOA</strong> lies in its excellent miscibility with epoxidized vegetable oils, providing low-viscosity mixtures that can be readily blended with other epoxy resins without requiring large amounts of solvent. Epoxidized soybean oil (<strong>ESBO</strong>) proved to be an efficient reactive diluent, reducing solvent use to trace levels. Cross-linked materials with glassy-state moduli in the gigapascal range, comparable to fossil-based thermosets, were obtained. These results establish <strong>EMPOA</strong> and <strong>EMPUA</strong> as promising dual-reactive monomers for the design of high-performance and fully biobased thermosetting materials.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (172KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 2191-2207"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224768","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 : 2026-03-09Epub Date: 2026-02-23DOI: 10.1021/acs.biomac.5c02130
Lena Zeroug-Metz , Kristela Shehu , Justine Bassil , Justin Podlecki , Philipp Sonntag , Marcus Koch , Anastasia Christoulaki , Eric Buhler , Anna K. H. Hirsch , Annette Kraegeloh , Marc Schneider , Sangeun Lee
Catechol-modified polymers, such as DOPA-functionalized systems, have recently gained significant interest for a variety of biomedical applications, particularly in their role as antibacterial adjuvants due to their oxidative activity and ability to generate reactive oxygen species (ROS). Current catechol-functionalized polymers, however, often suffer from a restricted number of catechol groups, limited biocompatibility and solubility, and low stability due to the rapid oxidation under physiological conditions. In this study, we developed a water-soluble, biocompatible DOPA-modified biodynamer (DOPA-BD), leveraging the principles of constitutional dynamic chemistry (CDC). DOPA-BD was synthesized via polycondensation of DOPA-hydrazide and the hexaethylene glycol-conjugated carbazole dialdehyde (CA-HG), forming dynamic imine and acylhydrazone linkages between the monomers. As a result of its dynamic covalent backbone, DOPA-BD exhibits biodegradability and undergoes pH-responsive degradation under mildly acidic conditions typically found at infection sites, leading to a more than 3-fold increase in DOPA-hydrazide release compared to physiological pH. Interestingly, driven by CDC, DOPA-BD folds into a nanorod structure with a hydrodynamic diameter of ∼7.8 nm, surrounded by HG chains that offer water solubility and biocompatibility. Moreover, the incorporation of the DOPA-derivative in each repeating unit yields a polymer with exceptionally high catechol content, which remains stable and resistant to oxidation for 72 h in physiological buffer conditions. Regarding its antibacterial applicability, DOPA-BD demonstrated synergistic antibacterial activity with Azithromycin (AZM) against AZM-resistant E. coli, enhancing the antibiotic’s efficacy by 4-fold. Our study indicates that DOPA-BD induces ROS production in the respective bacterial strain, suggesting ROS generation as one of the possible mechanisms contributing to the observed synergy. Overall, DOPA-BD represents a promising alternative strategy to potentiate antibacterial activity against resistant strains, holding strong potential for future antibacterial applications.
{"title":"Design of Poly-Catechol Biodynamers for Potentiation of Antibiotic Efficacy against Drug-Resistant Bacteria","authors":"Lena Zeroug-Metz , Kristela Shehu , Justine Bassil , Justin Podlecki , Philipp Sonntag , Marcus Koch , Anastasia Christoulaki , Eric Buhler , Anna K. H. Hirsch , Annette Kraegeloh , Marc Schneider , Sangeun Lee","doi":"10.1021/acs.biomac.5c02130","DOIUrl":"10.1021/acs.biomac.5c02130","url":null,"abstract":"<div><div>Catechol-modified polymers, such as DOPA-functionalized systems, have recently gained significant interest for a variety of biomedical applications, particularly in their role as antibacterial adjuvants due to their oxidative activity and ability to generate reactive oxygen species (ROS). Current catechol-functionalized polymers, however, often suffer from a restricted number of catechol groups, limited biocompatibility and solubility, and low stability due to the rapid oxidation under physiological conditions. In this study, we developed a water-soluble, biocompatible DOPA-modified biodynamer (DOPA-BD), leveraging the principles of constitutional dynamic chemistry (CDC). DOPA-BD was synthesized via polycondensation of DOPA-hydrazide and the hexaethylene glycol-conjugated carbazole dialdehyde (CA-HG), forming dynamic imine and acylhydrazone linkages between the monomers. As a result of its dynamic covalent backbone, DOPA-BD exhibits biodegradability and undergoes pH-responsive degradation under mildly acidic conditions typically found at infection sites, leading to a more than 3-fold increase in DOPA-hydrazide release compared to physiological pH. Interestingly, driven by CDC, DOPA-BD folds into a nanorod structure with a hydrodynamic diameter of ∼7.8 nm, surrounded by HG chains that offer water solubility and biocompatibility. Moreover, the incorporation of the DOPA-derivative in each repeating unit yields a polymer with exceptionally high catechol content, which remains stable and resistant to oxidation for 72 h in physiological buffer conditions. Regarding its antibacterial applicability, DOPA-BD demonstrated synergistic antibacterial activity with Azithromycin (AZM) against AZM-resistant E. coli, enhancing the antibiotic’s efficacy by 4-fold. Our study indicates that DOPA-BD induces ROS production in the respective bacterial strain, suggesting ROS generation as one of the possible mechanisms contributing to the observed synergy. Overall, DOPA-BD represents a promising alternative strategy to potentiate antibacterial activity against resistant strains, holding strong potential for future antibacterial applications.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 1949-1968"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275195","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 : 2026-03-09Epub Date: 2026-02-04DOI: 10.1021/acs.biomac.5c02659
Shichen Zhu , Ningning Peng , Rongrong Mu , Shulai Liu , Yuting Ding , Xuxia Zhou
In this work, the ice-inhibiting effects and their underlying mechanisms of inulin with various chain lengths were elucidated through experimental measurements and molecular dynamics simulations. The results suggested that long-chain inulin (HP group) exhibited strong and stable ice-inhibiting effects, with a minimum %MGS (12.18%) and limited ice growth of 36.61% after 100 min of freezing. The extensive contact area of long-chain inulin with water molecules (higher Rg and solvent-accessible surface area (SASA) values) favored their hydrogen-bond formation, which further disrupted the original hydrogen-bonding network of water by transforming the hydrogen-bonding mode (DDAA–OH mode into the DA mode). The remarkable cryoprotective effects of the HP group on scallops were evidenced by no significant difference in mass loss, water-holding capacity (WHC), and structural stability of the myofibrillar protein with the commercial antifreeze group (p > 0.05). This study provides strong evidence to broaden the cryoprotection applications of inulin to improve the quality of frozen food.
{"title":"Mechanism Unraveling the Ice-Inhibition Differences of Inulin with Varied Polymerization Degrees and Its Cryoprotective Effects on Frozen Scallops","authors":"Shichen Zhu , Ningning Peng , Rongrong Mu , Shulai Liu , Yuting Ding , Xuxia Zhou","doi":"10.1021/acs.biomac.5c02659","DOIUrl":"10.1021/acs.biomac.5c02659","url":null,"abstract":"<div><div>In this work, the ice-inhibiting effects and their underlying mechanisms of inulin with various chain lengths were elucidated through experimental measurements and molecular dynamics simulations. The results suggested that long-chain inulin (HP group) exhibited strong and stable ice-inhibiting effects, with a minimum %MGS (12.18%) and limited ice growth of 36.61% after 100 min of freezing. The extensive contact area of long-chain inulin with water molecules (higher <em>R</em> <sub>g</sub> and solvent-accessible surface area (SASA) values) favored their hydrogen-bond formation, which further disrupted the original hydrogen-bonding network of water by transforming the hydrogen-bonding mode (DDAA–OH mode into the DA mode). The remarkable cryoprotective effects of the HP group on scallops were evidenced by no significant difference in mass loss, water-holding capacity (WHC), and structural stability of the myofibrillar protein with the commercial antifreeze group (<em>p</em> > 0.05). This study provides strong evidence to broaden the cryoprotection applications of inulin to improve the quality of frozen food.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (177KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 3","pages":"Pages 2272-2282"},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111519","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}
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