{"title":"Multifunctional Nanoplatform Based on Gelatin Nanoparticles with Immunomodulatory Capabilities for Combined Immunotherapy and Chemotherapy of Melanoma.","authors":"Ying Chen, Miaomiao Zhang, Zongjia Li, Jinyao Zheng, Yuanhao Zhang, Qianyu Guo, Suzhen Liu, Yu Chen, Wei Wei, Xiue Jiang, Jilin Tang","doi":"10.1021/acs.biomac.5c00098","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00098","url":null,"abstract":"<p><p>Tumor immunotherapy has shown considerable therapeutic potential, especially when combined with chemotherapy. In this study, we developed a multifunctional nanoplatform GNPs-DOX/R848 that combined immunotherapy and chemotherapy for the treatment of melanoma, in which gelatin nanoparticles (GNPs) were loaded with the immunomodulatory agent resiquimod (R848) and the chemotherapy drug doxorubicin (DOX). GNPs possessed inherent immunomodulatory properties; when combined with R848, they induced a more pronounced polarization of M1-like macrophages by activating the NF-κB signaling pathway, thereby reversing the immunosuppressive tumor microenvironment. Meanwhile, GNPs effectively delivered R848 and DOX to tumor cells, promoting stronger therapeutic effects of the drugs, which strongly induced the immunogenic cell death triggered by DOX, leading to the infiltration of T cells into the tumor tissue. The treatment of melanoma demonstrated that GNPs-DOX/R848 significantly reduced tumor volume, enhanced the therapeutic effects of chemotherapy, providing a new approach for the combined treatment of cancer with immunotherapy and chemotherapy.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"2996-3010"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952399","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 : 2025-05-12Epub Date: 2025-04-29DOI: 10.1021/acs.biomac.5c00362
Alessandra Fusco, Anna Guarnieri, Carmen Scieuzo, Micaela Triunfo, Rosanna Salvia, Giovanna Donnarumma, Patrizia Falabella
{"title":"<i>Hermetia illucens</i>-Derived Chitosan: A Promising Immunomodulatory Agent for Applications in Biomedical Fields.","authors":"Alessandra Fusco, Anna Guarnieri, Carmen Scieuzo, Micaela Triunfo, Rosanna Salvia, Giovanna Donnarumma, Patrizia Falabella","doi":"10.1021/acs.biomac.5c00362","DOIUrl":"10.1021/acs.biomac.5c00362","url":null,"abstract":"<p><p>Chitosan, renowned for its important biological properties, is a valuable pharmaceutical excipient for different therapeutic approaches. Currently, the demand for the biopolymer on the market is growing, and, for this reason, it is important to biologically characterize the biopolymer produced from an alternative source to crustaceans, specifically the bioconverter insect <i>Hermetia illucens</i>. In this work, insect chitosan, yielded via heterogeneous and homogeneous deacetylation from larvae, pupal exuviae, and adults, was studied as an immunomodulatory agent. The inflammatory response of immortalized human keratinocyte cells was induced by <i>Salmonella enterica</i> subsp. <i>enterica</i> serovar Typhimurium lipopolysaccharide. After that, the ability of the biopolymer to reduce the expression of the pro-inflammatory cytokines IL-6, IL-8, IL-1α, and TNF-α was tested after 6 and 24 h of treatment. Insect chitosan samples effectively downregulated cytokine expression, with improved activity obtained from heterogeneous chitosan treatments.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"3224-3233"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-05-12Epub Date: 2025-05-01DOI: 10.1021/acs.biomac.5c00244
Diptomit Biswas, Sara Benson, Aidan Matunis, Gebremichal Gebretsadik, Adam Wertz, Ben J StPierre, Nathan Schacht, Yue Yan, Hanna Y Gebremichael, Pak Kin Wong, Anthony D Baughn, Scott H Medina
{"title":"Lead Informed Artificial Intelligence Mining of Antitubercular Host Defense Peptides.","authors":"Diptomit Biswas, Sara Benson, Aidan Matunis, Gebremichal Gebretsadik, Adam Wertz, Ben J StPierre, Nathan Schacht, Yue Yan, Hanna Y Gebremichael, Pak Kin Wong, Anthony D Baughn, Scott H Medina","doi":"10.1021/acs.biomac.5c00244","DOIUrl":"10.1021/acs.biomac.5c00244","url":null,"abstract":"<p><p>Identifying host defense peptides (HDPs) that are effective against drug-resistant infections is challenging due to their vast sequence space. Artificial intelligence (AI)-guided design can accelerate HDP discovery, but it traditionally requires large data sets to operationalize. We report an AI workflow that utilizes limited data sets (∼100 peptides) to uncover potent, selective, and safe HDPs by informing selection through lead candidate mutational scanning. This approach, referred to as Lead Informed Machine Interrogation of Therapeutic Sequences (LIMITS), is applied against the exemplary pathogen <i>Mycobacterium tuberculosis</i>. Experimental validation of predicted sequences shows nearly an order of magnitude improvement in potency, selectivity, and safety, relative to the initial template. Post hoc analysis suggests sequence length may be a unique and underappreciated driver of antitubercular HDP activity. These results demonstrate that, with continued development, the LIMITS approach can identify selective HDPs under data-limited conditions and elucidate structure-function-performance relationships previously hidden in biologic complexity.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"3167-3179"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-05-12Epub Date: 2025-04-06DOI: 10.1021/acs.biomac.5c00260
Yanli Xu, Fleur Ruijne, Manel Garcia Diez, Jorrit Jilles Stada, Oscar P Kuipers
{"title":"Design and Production of Geranylated Cyclic Peptides by the RiPP Enzymes SyncM and PirF.","authors":"Yanli Xu, Fleur Ruijne, Manel Garcia Diez, Jorrit Jilles Stada, Oscar P Kuipers","doi":"10.1021/acs.biomac.5c00260","DOIUrl":"10.1021/acs.biomac.5c00260","url":null,"abstract":"<p><p>The growing threat of antibiotic resistance highlights the urgent need for new antimicrobial agents. Nonribosomal peptides (NRPs) are potent antibiotics with complex structures, but generating novel NRP analogues is costly and inefficient. An emerging alternative is using ribosomally synthesized and post-translationally modified peptides (RiPPs), which are gene-encoded, allowing for easier mutagenesis and modification. This study aimed to produce peptides with two key structural elements of many NRP antibiotics: a macrocycle and an N-terminal lipid moiety. The RiPP enzymes SyncM and PirF were employed-SyncM introduced lanthionine or methyllanthionine macrocycles, while PirF incorporated isoprenyl chains to emulate the lipid moieties in NRPs. Both enzymes successfully modified the templates, and their combined use generated lipidated macrocyclic peptides, resembling lipopeptide antibiotics. These findings demonstrate the potential of SyncM and PirF as versatile tools for designing novel gene-encoded NRP mimics, enabling high-throughput screening for new bioactive peptides.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"3186-3199"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-05-12Epub Date: 2025-04-08DOI: 10.1021/acs.biomac.4c01651
Caterina Presutti, Edo Vreeker, Sajitha Sasidharan, Zanetta Ferdinando, Marc Stuart, Joanna Juhaniewicz-Dębińska, Giovanni Maglia, Wouter H Roos, Bert Poolman
{"title":"Balancing Permeability and Stability: A Study of Hybrid Membranes for Synthetic Cells Using Lipids and PBd-<i>b</i>-PEO Block Copolymers.","authors":"Caterina Presutti, Edo Vreeker, Sajitha Sasidharan, Zanetta Ferdinando, Marc Stuart, Joanna Juhaniewicz-Dębińska, Giovanni Maglia, Wouter H Roos, Bert Poolman","doi":"10.1021/acs.biomac.4c01651","DOIUrl":"10.1021/acs.biomac.4c01651","url":null,"abstract":"<p><p>We have synthesized hybrid membranes composed of amphiphilic block copolymers, polybutadiene-poly(ethylene oxide) [PBd-<i>b</i>-PEO], with different lengths [PBd<sub>22</sub>-PEO<sub>14</sub> and PBd<sub>11</sub>-PEO<sub>8</sub>] and mixtures of phospholipids (DOPC:DOPG:DOPE 50:25:25 mol %) to combine the properties of both in terms of stability and fluidity of the membrane. The amphiphilic block copolymers increase the stability, whereas the lipids support the functionality of membrane proteins. The hybrid nature of the bilayers was studied by means of Cryo-TEM, Langmuir-Blodgett technique, atomic force microscopy (AFM), electrical measurements, and fluorescence-based stopped-flow assay to determine the permeability of the membrane for water and osmolytes. We observe that the structural, thermodynamic, and permeability properties of hybrid PBd<sub>11</sub>-PEO<sub>8</sub> membranes are similar to their purely lipid counterparts, with the advantage of being more stable and resisting a higher transmembrane electrical potential. Hybrid membranes with the longer polymer, PBd<sub>22</sub>-PEO<sub>14</sub>, display more significant structural, thermodynamic, and permeability differences and show less favorable properties than hybrid-PBd<sub>11</sub>-PEO<sub>8</sub> membranes.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"2868-2881"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-05-12Epub Date: 2025-04-30DOI: 10.1021/acs.biomac.5c00280
Himanshu Polara, Tejas Shah, Godwin Babanyinah, Hanghang Wang, Abhi Bhadran, Michael C Biewer, Mihaela C Stefan
{"title":"Improved Drug Delivery through Amide-Functionalized Polycaprolactones: Enhanced Loading Capacity and Sustained Drug Release.","authors":"Himanshu Polara, Tejas Shah, Godwin Babanyinah, Hanghang Wang, Abhi Bhadran, Michael C Biewer, Mihaela C Stefan","doi":"10.1021/acs.biomac.5c00280","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00280","url":null,"abstract":"<p><p>Polymeric micelles are effective for drug delivery but often face instability, low drug loading capacity (DLC), and premature drug leakage. Herein, we report that disubstituted γ-amide functionalized ε-caprolactone (ε-CL) monomers double the substituent density per polymeric unit, enhancing micelle properties and improving drug delivery applications. Three hydrophobic ε-CL monomers with two propyl groups, two benzyl groups, and a combination of propyl and benzyl groups were synthesized. The obtained monomers were polymerized by ring-opening polymerization using poly(ethylene glycol) (PEG) as a macroinitiator and the hydrophilic block. The synthesized copolymers successfully self-assembled to form micelles, and doxorubicin (DOX) was loaded into all micelles. Poly(ethylene glycol)<i>-b-</i>poly(<i>N</i>-propyl-<i>N</i>-benzyl-7-oxopane-4-carboxamide) (PEG<i>-b-</i>PBnPyCL) exhibited 7.33 wt % DLC with pH-responsive drug release in acidic conditions. In addition, the DOX-loaded micelles of PEG-<i>b</i>-PBnPyCL exhibited nearly 20% cell viability in MDA-MB-231 cancer cells. These results contribute to advancing polymeric micelles as drug carriers with clinical translation potential.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"3213-3223"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951548","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 : 2025-05-12Epub Date: 2025-04-06DOI: 10.1021/acs.biomac.4c01707
Wafaa Aljuhani, Matthew P Wylie, Rudra N Purusottam, Colin P McCoy, Steven E J Bell
{"title":"Probing the Coupled Equilibria between Metal Nanoparticles, Antibiotics and Components of the Extracellular Matrix in Biofilms with SERS.","authors":"Wafaa Aljuhani, Matthew P Wylie, Rudra N Purusottam, Colin P McCoy, Steven E J Bell","doi":"10.1021/acs.biomac.4c01707","DOIUrl":"10.1021/acs.biomac.4c01707","url":null,"abstract":"<p><p>Understanding the interplay between nanoparticles, biomaterials and drug molecules in biological environments is important but studying these interactions in complex systems such as biofilms is challenging. Here, surface-enhanced Raman spectroscopy (SERS) with gold nanostars (NS) was used to monitor how biofilm components influence the binding and SERS signals of two antibiotics, levofloxacin (Levo) and ampicillin (Amp). The SERS signals of both antibiotics were reduced by approximately 70% (Levo) and 90% (Amp) in biofilm environments. Investigations of mixtures of model biofilm components: adenine (nucleic acids), alginate (polysaccharides) and albumin (proteins), revealed that their interactions with NS are governed by coupled equilibria. This gave surprising results, for example, alginate reduced the interference from adenine and albumin, so adding alginate increased the intensity of the antibiotic signals 4x. These findings highlight the importance of matrix component interactions in modulating detection sensitivity and show that these effects are critical in allowing clinically relevant detection levels to be achieved.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"2900-2908"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-05-12Epub Date: 2025-04-18DOI: 10.1021/acs.biomac.5c00121
Yuta Komano, Miho Suzuki, Takahiko Matsushita, Tetsuo Koyama, Yoshihiro Ishimaru, Ken Hatano, Koji Matsuoka
{"title":"Synthesis of Water-Soluble Glycopolymers Bearing Porphyrin by Means of Glycopolymer Assembly and Physical Properties of Glycopolymers Including Ability for Singlet Oxygen Production.","authors":"Yuta Komano, Miho Suzuki, Takahiko Matsushita, Tetsuo Koyama, Yoshihiro Ishimaru, Ken Hatano, Koji Matsuoka","doi":"10.1021/acs.biomac.5c00121","DOIUrl":"10.1021/acs.biomac.5c00121","url":null,"abstract":"<p><p>Although photodynamic therapy (PDT) is expected to offer advantages in terms of selectivity, increased efficacy, and reduced side effects, the low solubilities of photosensitizers in aqueous media are significant issues. In this study, porphyrin-based monomers were synthesized by acryloylation of known tetraphenylporphyrin [5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin] (TPP). Simple radical polymerization of the porphyrin monomer and known glycosyl monomers in the presence of acrylamide to avoid steric hindrance yielded the corresponding polymeric photosensitizers, water-soluble glycopolymers with porphyrin moieties. The introduction of a porphyrin core gave polymer fluorescence and reactive oxygen species generation properties, and the addition of d-lactose and <i>N</i>-acetyl-d-glucosamine, respectively, remarkably improved solubility in water. The glycopolymers had high optical absorption, emission, and excitation in the visible light range and a singlet oxygen (SO) generation characteristic of porphyrins in aqueous solution, suggesting incorporation of the TPP into the linear polymer. The glycopolymers are promising not only for PDT but also as anticancer agents.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"3021-3031"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthesis of Flexible Random Copolymers of Poly(butylene <i>trans</i>-1,4-ciclohexanedicarboxylate) Containing Pripol Moiety as Potential Candidates for Vascular Applications: Solid-State Characterization and Preliminary <i>In Vitro</i> Biocompatibility and Hemocompatibility.","authors":"Edoardo Bondi, Nora Bloise, Michelina Soccio, Giulia Guidotti, Ilenia Motta, Massimo Gazzano, Marco Ruggeri, Lorenzo Fassina, Emilia Genini, Livia Visai, Gianandrea Pasquinelli, Nadia Lotti","doi":"10.1021/acs.biomac.4c01668","DOIUrl":"10.1021/acs.biomac.4c01668","url":null,"abstract":"<p><p>In order to envisage new solutions for complications associated with cardiovascular diseases, including the occlusion of small vessels, a family of random copolymers of poly(butylene <i>trans</i>-1,4-ciclohexanedicarboxylate) (PBCE), containing Pripol moiety, namely, poly(butylene <i>trans</i>-1,4-ciclohexaendicarboxylate/Pripol), were successfully synthesized. The copolymers display reduced crystallinity and stiffness compared with PBCE, exhibiting elastic modulus values that are comparable to those of materials previously investigated for similar applications. The stability of the materials under physiological conditions was demonstrated over an extended time. Cytotoxicity was confirmed by a direct contact assay with human umbilical vein endothelial cells (HUVECs), and blood compatibility was established by the absence of any change in the values of activated prothrombin time and activated partial thromboplastin time, in addition to the low adhesion of blood components. The results demonstrated that the ad hoc design is pivotal in regulating solid state and functional properties, thereby facilitating the development of innovative materials for vascular tissue engineering.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"2882-2899"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomacromoleculesPub Date : 2025-05-12Epub Date: 2025-04-21DOI: 10.1021/acs.biomac.4c01110
Sabrina Roussel, Lucia Carrera Fragoso, Philippe Grenier, Quentin Bruxelles, Valérie Chénard, Sébastien Marcoux, Karine Greffard, Sébastien Fortin, Luc Vallières, Nicolas Bertrand
{"title":"Glycerol-Based Polymer to Improve the Cellular Uptake of Liposomes.","authors":"Sabrina Roussel, Lucia Carrera Fragoso, Philippe Grenier, Quentin Bruxelles, Valérie Chénard, Sébastien Marcoux, Karine Greffard, Sébastien Fortin, Luc Vallières, Nicolas Bertrand","doi":"10.1021/acs.biomac.4c01110","DOIUrl":"10.1021/acs.biomac.4c01110","url":null,"abstract":"<p><p>Nanomedicines modify the pharmacology of pharmaceutical ingredients, but most require cell internalization to deliver their payloads. Hence, modifying the surface properties of nanomedicines can improve their interactions with cells and modulate their pharmacology. Herein, we devised a polymer that increases how nanomedicines are internalized by cells. The alkylated poly(monoglycerol acrylate) (PMGA) polymer was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization with a terminal double 18-carbon moiety that allows its anchoring on the surface of liposomes. PMGA-decorated liposomes are internalized more efficiently in immune cells, compared to formulations without the polymer. Using inhibitors of internalization pathways, we established that PMGA promotes cell entry by the fast endophilin-mediated endocytosis (FEME). In comparison, noncoated control liposomes were mostly internalized by clathrin-mediated endocytosis. This work highlights the potential of PMGA to increase the internalization of nanomedicines by immune cells, and target a novel internalization pathway.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 5","pages":"2811-2824"},"PeriodicalIF":5.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}