BiomacromoleculesPub Date : 2025-07-03DOI: 10.1021/acs.biomac.5c00283
Ozgul Gok, Anjali Sharma, Siva P Kambhampati, Elizabeth Smith Khoury, Sujatha Kannan, Rangaramanujam M Kannan
{"title":"Sustained and Step-Wise Drug Release by a Novel Double Responsive Dendrimer-<i>N</i>-Acetylcysteine Conjugate.","authors":"Ozgul Gok, Anjali Sharma, Siva P Kambhampati, Elizabeth Smith Khoury, Sujatha Kannan, Rangaramanujam M Kannan","doi":"10.1021/acs.biomac.5c00283","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00283","url":null,"abstract":"<p><p>Polyamidoamine (PAMAM) dendrimers have emerged as promising vehicles for targeting the brain due to their intrinsic ability to penetrate through the injured blood-brain barrier. Herein, we present a novel drug delivery system based on a fourth generation PAMAM dendrimer as a brain targeting nanomedicine for the delivery of an anti-inflammatory drug <i>N</i>-acetyl cysteine with a sustained drug release profile. This D<sub>\"ester\"</sub>(NAC<sub>\"ss\"</sub>NAC) design enables NACs conjugated to the periphery of PAMAM dendrimers in the dimer form with ester and disulfide bonds to be sequentially released in a stepwise manner, responding to environmental pH and redox potential. Moreover, in vitro studies were conducted with a fluorescently labeled conjugate to confirm its nontoxic behavior and time-dependent cellular uptake, together with improved anti-inflammatory and antioxidative effects over endotoxin-activated microglia. These findings demonstrate that the DNACNAC conjugate has a high potential to be utilized as a promising dendrimer-based nanomedicine platform for prolonged treatment of neuroinflammation-related CNS disorders.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Ferrocene-Based Supramolecular Photothermal Agent for Enhanced Photothermal/Ferroptosis Therapy and Immune Activation.","authors":"Jing Qian, Duoduo Jiang, Zepeng Cui, Dmitri Krysko, Jia Tian, Weian Zhang","doi":"10.1021/acs.biomac.5c00464","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00464","url":null,"abstract":"<p><p>Photothermal therapy (PTT) is impeded by limited light penetration depth and cellular heat resistance induced by overexpressed heat shock proteins. Herein, we propose a ferrocene (Fc)-based supramolecular photothermal agent (PTA) to improve the therapeutic efficacy. Cy-Fc/CD-PEG not only had excellent photothermal effect but also possessed the ability to induce ferroptosis and immunotherapy. Cy-Fc/CD-PEG released Fc under intracellular acidic conditions. Then the Fe<sup>2+</sup> of Fc could react with endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to generate hydroxyl radicals (<sup>•</sup>OH) and Fe<sup>3+</sup>. The generated Fe<sup>3+</sup> could be reduced to Fe<sup>2+</sup> by depletion of intracellular glutathione (GSH), which promoted reactive oxygen species (ROS) generation via triggering the Fenton reaction and consuming GSH, leading to ferroptosis. Meanwhile, apoptotic tumor cells released abundant tumor-associated antigens, activating antitumor immunity. Both <i>in vitro</i> and <i>in vivo</i> experiments demonstrated excellent antitumor effects by the ferrocene-based Cy-Fc/CD-PEG supramolecular PTA. This work provided a PTT-ferroptosis combination strategy that activated antitumor immunity and inhibited tumor growth.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558424","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}
BiomacromoleculesPub Date : 2025-07-03DOI: 10.1021/acs.biomac.5c00441
Kan Cheng, Tao Liu, Simeng Gao, Fangfang Niu, Xueli Wang, Jianyong Yu, Yanping Wang, Shuohan Huang, Yong He
{"title":"Synthesis, Characterization, and Degradation on the Quasi-Alternating Polyester Amides Derived from ε-Caprolactone, Diamine, and Diacid.","authors":"Kan Cheng, Tao Liu, Simeng Gao, Fangfang Niu, Xueli Wang, Jianyong Yu, Yanping Wang, Shuohan Huang, Yong He","doi":"10.1021/acs.biomac.5c00441","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00441","url":null,"abstract":"<p><p>Poly(ε-caprolactone) (PCL) has been widely studied due to its excellent biodegradability and biocompatibility. However, its low melting temperature (∼60 °C) and limited tensile strength (∼10 MPa) restrict its application in high-performance or thermally demanding environments. To overcome these limitations, we developed a novel two-step melt polycondensation strategy to synthesize quasi-alternating poly(ester amide)s (PEAs) by incorporating diamide diols derived from ε-caprolactone. This synthetic approach enables precise control over the polymer microstructure, leading to PEAs with tunable crystallinity, enhanced chain regularity, and improved segmental interactions. The successful synthesis of PEAs was confirmed using nuclear magnetic resonance and infrared spectroscopy. The results demonstrate that PEAs possess adjustable melting temperatures (<i>T</i><sub>m</sub> = 134-139 °C), moderate crystallinity (<i>X</i><sub>c</sub> = 17-35%), excellent transparency (<i>T</i> > 85%), tensile strength (15-18 MPa), and high elongation at break (ε = 68-800%). This work offers a promising route toward high-performance, sustainable materials for packaging and biomedical applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551432","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}
BiomacromoleculesPub Date : 2025-07-03DOI: 10.1021/acs.biomac.5c00522
Ho Young Lee, Joonseok Lee, Wonsik Eom, Won Jun Lee
{"title":"Capillary Migration of Peptide Nanowires for Surface Strengthening.","authors":"Ho Young Lee, Joonseok Lee, Wonsik Eom, Won Jun Lee","doi":"10.1021/acs.biomac.5c00522","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00522","url":null,"abstract":"<p><p>This study explores the capillarity-guided self-assembly of cyclo-diphenylalanine (FF) nanowires on surface defects with engineered topographies, emphasizing the interplay between geometric confinement and evaporation-driven flow. Evaporation on v-groove and trench substrates induces directional migration and alignment of FF nanowires, forming ordered, surface-adherent structures. Numerical simulations support these observations by illustrating flow behavior and deposition patterns. Guided by this mechanism, we fabricated nanowire-reinforced polyvinyl alcohol (PVOH) composite fibers with high stiffness (20.29 ± 6.57 GPa) and tensile strength (581.7 ± 34.69 MPa) at 10 wt % loading. Thermally treated, physically damaged fibers exhibited autonomous healing without external agents. Capillary migration and nanowire reassembly at fracture interfaces restored continuity and improved ductility, reflecting dynamic nanowire organization. These results present a geometric strategy for nanowire alignment and demonstrate the dual function of peptide nanowires in mechanical reinforcement and self-repair, highlighting their potential as active components in bioinspired, damage-tolerant materials.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Designing Self-Healing Hydrogels with Antibacterial Property Based on Host-Guest Interactions between Aminoazobenzene-Modified Gelatin and Polycyclodextrin for Prolonging the Shelf Life of Tyrosinase Enzyme.","authors":"Shaghayegh Vakili, Hamed Azadfar, Ebrahim Ahmadi, Zahra Mohamadnia, Atiyeh Mahdavi, Faezeh Hanifeh","doi":"10.1021/acs.biomac.5c00346","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00346","url":null,"abstract":"<p><p>Here, a self-healing hydrogel was designed and synthesized to immobilize tyrosinase enzyme (Tyr), addressing the need for improved enzyme performance. The self-healing properties of the hydrogel ensured structural integrity, while its enzyme immobilization capability significantly enhanced enzyme stability and activity. The hydrogel was synthesized via host-guest interactions between polycyclodextrin (PCD) and aminoazobenzene-modified gelatin (Gel-AZO), and chemically cross-linked in the presence of glycidyl methacrylate-modified gelatin (GM-Gelatin) and acryloyloxyethyltrimethylammonium chloride (DAC) to form a dual-network structure. The immobilized enzyme retained 94.56% of the free enzyme's activity and remained stable under varying pH and temperatures, maintaining 70% activity at 70 °C. Reusability tests showed preserved enzymatic activity over six cycles. The hydrogel exhibited antibacterial activity against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, maintained cell viability above 80%, and showed hemolytic activity below 5%. These results highlight the potential applicability of this self-healing hydrogel in biomedical and industrial settings that require stable enzymatic performance.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551430","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}
BiomacromoleculesPub Date : 2025-07-01DOI: 10.1021/acs.biomac.5c00479
Yifan Lu, Bo Chen, Xiangxin Lou, Yi Li, Jinglei Wu, Haochen Yao, Bei Feng
{"title":"Ibuprofen Conjugated Epsilon-poly-l-lysine Methacrylate Hydrogel Modulates Macrophage Polarization and Mitigates Inflammation <i>In Vivo</i>.","authors":"Yifan Lu, Bo Chen, Xiangxin Lou, Yi Li, Jinglei Wu, Haochen Yao, Bei Feng","doi":"10.1021/acs.biomac.5c00479","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00479","url":null,"abstract":"<p><p>Epsilon-poly-l-lysine (EPL) is widely used in many biomedical applications due to its excellent antibacterial activity and good biocompatibility. In this study, we report an approach of carbodiimide chemistry to graft water-soluble EPL with hydrophobic drug ibuprofen (IBU) and then modify the obtained IBU-EPL conjugate with methacrylic anhydride (MA) to prepare IBU-EPL-MA. The IBU-EPL-MA was of good photo-cross-linkability to form hydrogel with sustained drug release and good blood compatibility. It significantly inhibited bacterial growth, promoted lipopolysaccharide (LPS)-induced macrophage polarization to the M2-like phenotype, and reduced reactive oxygen species (ROS) levels <i>in vitro</i>. The IBU-EPL-MA hydrogel elicited milder foreign body response (FBR) as evidenced by reduced fibrous capsule thickness, increased macrophage polarization to M2-like phenotype, and less extent of blood vessel formation surrounding implants in a mouse subcutaneous model. This study provides insights into multifunctional EPL-based biomaterials with antibacterial, anti-inflammatory, and sustained drug release capabilities that expand potential biomedical applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537399","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}
BiomacromoleculesPub Date : 2025-07-01DOI: 10.1021/acs.biomac.5c01010
Juan Cruz Almada, Miguel Marco-Martin, David Roura-Padrosa, Susana Velasco-Lozano
{"title":"Immobilization of Thrombin on Agarose-Based Supports for Affinity Tag Removal.","authors":"Juan Cruz Almada, Miguel Marco-Martin, David Roura-Padrosa, Susana Velasco-Lozano","doi":"10.1021/acs.biomac.5c01010","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c01010","url":null,"abstract":"<p><p>Thrombin, a specific serine protease, is essential in recombinant protein purification by removing affinity tags. However, its soluble form has drawbacks like instability, contamination, and limited reusability. This study explores the covalent immobilization of bovine thrombin to enhance its performance as a reusable biocatalyst. Using the CapiPy tool, surface residues suitable for immobilization on agarose supports were identified. Thrombin immobilized on glyoxyl-activated agarose showed optimal results, efficiently removing 6xHis-tags from recombinant proteins with activity comparable to the soluble enzyme. It also cleaved other peptide tags, underscoring its versatility. It retained full activity after 1.5 h at 50 °C, while the soluble form was almost inactivated. The immobilized enzyme maintained consistent performance over 10 batch cycles and achieved a space-time yield of 4.7 g·L<sup>-1</sup>·h<sup>-1</sup>. These findings highlight the potential of immobilized thrombin as a robust and cost-effective tool to improving recombinant protein purification workflows, with significant implications for both industrial and research applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537400","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}
BiomacromoleculesPub Date : 2025-07-01DOI: 10.1021/acs.biomac.5c00378
Qipeng Yan, Xingyue Jiang, Wei Xie, Xia Wu, Dalian Gong, Zenghui Li, Dan Yuan, Junfeng Shi
{"title":"Enhanced Intracellular Delivery by Twisted CC-Loop Conformation in Cyclic Cell-Penetrating Peptides.","authors":"Qipeng Yan, Xingyue Jiang, Wei Xie, Xia Wu, Dalian Gong, Zenghui Li, Dan Yuan, Junfeng Shi","doi":"10.1021/acs.biomac.5c00378","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00378","url":null,"abstract":"<p><p>Biological drugs hold great promise for treating various diseases, but their efficacy is often limited by poor cellular uptake. Herein, we introduce cyclic cell-penetrating peptides (CPPs) to enhance the delivery efficiency. Three cyclic peptides with varying ring sizes were designed from a classic amphiphilic CPP <i>via</i> disulfide bond formation. Among them, <b>Y</b><sub><b>2-13</b></sub><b>-OX</b> adopted a twisted CC-loop conformation distinct from the typical β-hairpin on negatively charged cell surfaces. This unique structure enhanced membrane penetration, enabling superior delivery compared with linear and other cyclic variants. <b>Y</b><sub><b>2-13</b></sub><b>-OX</b> efficiently delivered functional siRNA targeting METTL3, achieving knockdown comparable to that of Lipofectamine 2000. It also transported GFP and plasmids, demonstrating versatility. Computational analysis revealed molecular-level insights into the enhanced interaction between the CC-loop structure and membranes. These findings establish a new CPP conformation that advances therapeutic delivery and opens new avenues for drug transport strategies.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537398","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}
BiomacromoleculesPub Date : 2025-06-28DOI: 10.1021/acs.biomac.5c00128
Saeed Davoodi, Faridah Namata, Tomas Rosén, Stephan V Roth, Michael Malkoch, L Daniel Söderberg, Fredrik Lundell
{"title":"Tuning Alignment, Strength, and Toughness in Functional Cellulose:Helux Filaments: A Molecular Trade-Off.","authors":"Saeed Davoodi, Faridah Namata, Tomas Rosén, Stephan V Roth, Michael Malkoch, L Daniel Söderberg, Fredrik Lundell","doi":"10.1021/acs.biomac.5c00128","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00128","url":null,"abstract":"<p><p>The complex architecture of wood motivates studies of bioinspired materials that combine strength, toughness, and mechanical integrity. We explore the interplay between nanofiber alignment and molecular interactions in composite filaments formed from cellulose nanofibers (CNFs) and a dendritic polyampholyte, Helux. Helux enhances strength by 60% and increases toughness 5-fold through ionic bonding and thermal covalent cross-linking. However, wide-angle X-ray scattering (WAXS) reveals reduced nanofiber alignment in Helux-containing samples, resulting in a 25% decrease in stiffness─highlighting a trade-off between structural order and cohesion. Polarized optical microscopy (POM) and in situ small-angle X-ray scattering (SAXS) attribute this reduced alignment to enhanced rotary diffusion, driven by carboxylate groups of the Helux. With Helux, multivalent links across the nanofibers give a denser and tougher network with fewer voids. This behavior resembles lignin and hemicellulose interactions in wood, where flexibility and cohesion govern the performance.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525408","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}