Biomacromolecules最新文献

{"title":"Site-Selective Zwitterionic Poly(caprolactone-carboxybetaine)-Growth Hormone Receptor Antagonist Conjugate: Synthesis and Biological Evaluation.","authors":"Jane Yang, Madeline B Gelb, Kyle Tamshen, Neil L Forsythe, Jeong Hoon Ko, Ellie G Puente, Emma Pelegri-O'Day, Stephen M F Jamieson, Jo K Perry, Heather D Maynard","doi":"10.1021/acs.biomac.4c00828","DOIUrl":"10.1021/acs.biomac.4c00828","url":null,"abstract":"<p><p>Zwitterionic polymers have been found to be biocompatible alternatives to poly(ethylene glycol) (PEG) for conjugation to proteins. This work reports the site-selective conjugation of poly(caprolactone-carboxybetaine) (pCLZ) to human growth hormone receptor antagonist (GHA) B2036-alkyne and investigation of safety, activity, and pharmacokinetics. Azide-end-functionalized pCLZs were synthesized and conjugated to GHA B2036-alkyne via copper-catalyzed click reaction. The resulting inhibitory bioactivity concentration responses in Ba/F3-GHR cells were compared to those of PEGylated GHA B2036. IgG and IgM antibody production was tested in mice, and no measurable antibody or cytokine production was detected for the pCLZ conjugate. Using ¹⁸F-labeled PET/CT imaging, the pCLZ conjugate showed an increase in circulation time compared to that of GHA B2036. Acute toxicity of the polymer was investigated in vivo and found to be nontoxic. Ex vivo degradation of the polymer on the conjugate was investigated. The results suggest that pCLZ-GHA is a potentially safe alternative to PEG-GHA.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542855","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":"Tumor Receptor-Mediated Morphological Transformation and <i>In Situ</i> Polymerization of Diacetylene-Containing Lipidated Peptide Amphiphile on Cell Membranes for Tumor Suppression.","authors":"Niannian Lv, Zhuo-Ran Yang, Jing-Wen Fan, Teng Ma, Kehan Du, Huimin Qin, Hao Jiang, Jintao Zhu","doi":"10.1021/acs.biomac.4c00936","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c00936","url":null,"abstract":"<p><p><i>In situ</i> polymerization on cell membranes can decrease cell mobility, which may inhibit tumor growth and invasion. However, the initiation of radical polymerization traditionally requires exogenous catalysts or free radical initiators, which might cause side effects in normal tissues. Herein, we synthesized a Y-type diacetylene-containing lipidated peptide amphiphile (TCDA-KFFFFK(GRGDS)-YIGSR, Y-DLPA) targeting integrins and laminin receptors on murine mammary carcinoma 4T1 cells, which underwent nanoparticle-to-nanofiber morphological transformation and <i>in situ</i> polymerization on cell membranes. Specifically, the polymerized Y-DLPA induced 4T1 cell apoptosis and disturbed the substance exchange and metabolism. <i>In vitro</i> assays demonstrated that the polymerized Y-DLPA nanofibers decreased the migration capacity of 4T1 cells, potentially suppressing tumor invasion and metastasis. When administered locally to 4T1 tumor-bearing mice, the Y-DLPA nanoparticles formed a biomimetic extracellular matrix that effectively suppressed tumor growth. This study provides an <i>in situ</i> polymerization strategy that can serve as an effective drug-free biomaterial with low side effects for antitumor therapy.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491099","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":"Genipap Oil as a Natural Cross-Linker for Biodegradable and Low-Ecotoxicity Porous Absorbents via Reactive Extrusion.","authors":"Liliana B Hurtado, Mercedes Jiménez-Rosado, Maryam Nejati, Faiza Rasheed, Thomas Prade, Amparo Jiménez-Quero, Marcos A Sabino, Antonio J Capezza","doi":"10.1021/acs.biomac.4c00883","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c00883","url":null,"abstract":"<p><p>Proteins derived from agroindustrial coproducts and a natural cross-linking agent (genipap oil containing genipin) were used to develop porous materials by reactive extrusion for replacing fossil-based absorbents. Incorporating genipap oil allowed the production of lightweight structures with high saline uptake (above 1000%) and competing retention capacity despite their porous nature. The mechanical response of the genipap-cross-linked materials was superior to that of the noncross-linked ones and comparable to those cross-linked using commercial genipin. The extruded products were hemocompatible and soil-biodegradable in less than 6 weeks. The compounds generated by the degradation process were not found to be toxic to the soil, showing a high bioassimilation capacity by promoting grass growth. The results demonstrate the potential of biopolymers and new green cross-linkers to produce fully renewable-based superabsorbents in hygiene products with low ecotoxicity. The study further promotes the production of these absorbents using low-cost proteins and continuous processing such as reactive extrusion.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491091","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":"Exploring the Interaction of Human α-Synuclein with Polyethylene Nanoplastics: Insights from Computational Modeling and Experimental Corroboration.","authors":"Neha Tripathi, Florent Saudrais, Mona Rysak, Laura Pieri, Serge Pin, Guido Roma, Jean-Philippe Renault, Yves Boulard","doi":"10.1021/acs.biomac.4c00918","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c00918","url":null,"abstract":"<p><p>Plastics, particularly microplastics (MPs) and nanoplastics (NP), have become major environmental and health concerns due to their high chemical stability. The highly hydrophobic plastics enter living organisms through reversible interactions with biomolecules, forming biocoronas. Following recent reports on plastics breaching the blood-brain barrier, the binding behavior of human α-synuclein (hαSn) with polyethylene-based (PE) plastics was evaluated by using molecular dynamics simulations and experimental methods. The results provided three important findings: (i) hαSn transitions from an open helical to a compact conformation, enhancing intramolecular interactions, (ii) nonoxidized PE NPs (NPnonox) rapidly adsorb hαSn, as supported by experimental data from dynamic light scattering and adsorption isotherms, altering its structure, and (iii) the oxidized NP (NPox) failed to capture hαSn. These interactions were dominated by the N-terminal domain of hαSn, with major contributions from hydrophobic amino acids. These findings raise concerns about the potential pharmacological effects of NP-protein interactions on human health.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491089","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":"Effects of Secondary Amine and Molecular Weight on the Biological Activities of Cationic Amphipathic Antimicrobial Macromolecules.","authors":"Zeyu Shao, Hao Luo, Thi Hanh Quyen Nguyen, Edgar H H Wong","doi":"10.1021/acs.biomac.4c01137","DOIUrl":"10.1021/acs.biomac.4c01137","url":null,"abstract":"<p><p>Cationic amphipathic antimicrobial agents inspired by antimicrobial peptides (AMPs) have shown potential in combating multidrug-resistant bacteria because of minimal resistance development. Here, this study focuses on the development of novel cationic amphipathic macromolecules in the form of dendrons and polymers with different molecular weights that employ secondary amine piperidine derivative as the cationic moiety. Generally, secondary amine compounds, especially at low molecular weights, have stronger bacteriostatic, bactericidal, and inner membrane disruption abilities than those of their primary amine counterparts. Low molecular weight <b>D2</b> dendrons with two cationic centers and one hydrophobic dodecyl chain produce outstanding synergistic activity with the antibiotic rifampicin against <i>Escherichia coli</i>, where one-eighth of the standalone dose of <b>D2</b> dendrons could reduce the concentration of rifampicin required by up to 4000-fold. The low molecular weight compounds are also less toxic and therefore have higher therapeutic index values compared to compounds with larger molecular weights. This study thus reveals key information that may inform the design of future synthetic AMPs and mimics, specifically, the design of low-molecular-weight compounds with secondary amine as the cationic center to achieve high antimicrobial potency and biocompatibility.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"6899-6912"},"PeriodicalIF":5.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277303","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":"Curdlan-Mediated Syngeneic RNAi against NF-κB in Glial Cells Protects Cerebral Vessels in the TBI Mouse Model.","authors":"Ruijun Wang, Wunile Zhu, Nuomin Bai, Muben Li, Saqirila Saqirila, Hangai Bai, Hai Xiao, Huricha Baigude, Naikang Gao","doi":"10.1021/acs.biomac.4c01001","DOIUrl":"10.1021/acs.biomac.4c01001","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) activates the NF-κB pathway in microglia and astrocytes, which secrete pro-inflammatory cytokines that disrupt the blood-brain barrier (BBB). Curdlan derivatives are promising carriers for the delivery of siRNA drugs. Herein, we evaluated the glial cell specificity, siRNA delivery efficiency, and the subsequent phenotypic regulation of glial cells by the Curdlan derivatives in the TBI mouse model. Our <i>in vitro</i> and <i>in vivo</i> studies confirmed that the (1) pAVC4 or CuMAN polymer encapsulating siRNA were internalized by astrocytes and microglia in a receptor-dependent manner; (2) systemic administration of the pAVC4 or CuMAN polymer encapsulating siRNA resulted in significant gene silencing efficiency, altered the phenotypic polarization of glial cells, and regulated the secretion of inflammatory cytokines; (3) this lessened neuroinflammation, ameliorated BBB destruction, and improved vascular recovery. These data suggested that pAVC4 and CuMAN polymers are promising RNA delivery vehicles that can efficiently deliver siRNA to the target cells.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"6780-6790"},"PeriodicalIF":5.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337321","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":"Accelerated Ten-Gram-Scale Synthesis of One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer 97.","authors":"Mahwish Arshad, Elena N Atochina-Vasserman, Srijay S Chenna, Devendra S Maurya, Muhammad Irhash Shalihin, Dipankar Sahoo, Alec C Lewis, Jordan J Lewis, Nathan Ona, Jessica A Vasserman, Houping Ni, Wook-Jin Park, Drew Weissman, Virgil Percec","doi":"10.1021/acs.biomac.4c01107","DOIUrl":"10.1021/acs.biomac.4c01107","url":null,"abstract":"<p><p>One-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimers (IAJDs) were discovered in our laboratories in 2021 to represent a new class of synthetic vectors for the targeted delivery of messenger RNA (mRNA). They coassemble with mRNA by simple injection of their ethanol solution into a pH 4 acetate buffer containing the nucleic acid into monodisperse dendrimersome nanoparticles (DNPs) with predictable dimensions. DNPs are competitive with 4-component lipid nanoparticles (LNPs), which are used in commercial COVID-19 vaccines, except that IAJDs are prepared in fewer reaction steps than each individual component of the LNPs. This simple methodology for the synthesis of IAJDs and their coassembly with mRNA into DNPs, together with the precise placement of their individual components and indefinite stability at room temperature in air, make them attractive candidates for the development of nanomedicine-based targeted mRNA delivery. Access to the large-scale synthesis of IAJDs without the need for sophisticated technologies, instrumentation, and synthetic skills is expected to open numerous new opportunities worldwide in nanomedicine. The goal of this publication is to report an accelerated ten-gram-scale synthesis of IAJD97 from inexpensive food additives obtained from renewable plant phenolic acid starting materials by methodologies accessible to any laboratory. This accelerated synthesis can be accomplished in 4 days. We expect that the work reported here will impact the field of nanomedicine in both developed and less developed countries.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"6871-6882"},"PeriodicalIF":5.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370192","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":"Label-Free Tracking of Hepatitis B Virus Core Protein Capsid Assembly in Real-Time Using Protein Charge Transfer Spectra.","authors":"Shah Ekramul Alom, Karthik Swaminathan, V Nuzelu, Alka Singh, Hugues de Rocquigny, Rajaram Swaminathan","doi":"10.1021/acs.biomac.4c00521","DOIUrl":"10.1021/acs.biomac.4c00521","url":null,"abstract":"<p><p>Hepatitis B virions are double-shelled particles, with a diameter of 40-42 nm, consisting of a nucleocapsid called the HBV core protein (HBV Cp). It is an ordered assembly of 90-120 homodimers arranged in an icosahedral symmetry. Both the full-length HBV Cp and the first-149 residue domain, HBV Cp149, can spontaneously assemble in vitro into capsids with 120 Cp dimers (<i>T</i> = 4) or 90 Cp dimers (<i>T</i> = 3), triggered by high ionic strength of 0.25-0.5 M NaCl. The assembly disassembly of HBV Cp149 capsids are generally studied by light scattering, size-exclusion chromatography, atomic force microscopy, transmission electron microscopy, and other high-end expensive techniques. Here, we report a simple, yet robust, label-free technique exploiting protein charge transfer spectra (ProCharTS) to monitor the capsid assembly in real-time. ProCharTS absorption in the near UV-visible region (250-800 nm) arises when photoinduced electron transfer occurs from HOMO of COO^- in glutamate (<i>donor</i>) to LUMO of NH₃⁺ in lysine <i>or</i> polypeptide backbone (<i>acceptor</i>) of the protein. Alternatively, it can also occur from polypeptide backbone (<i>donor</i>) to <i>acceptor</i> in arginine, histidine, or lysine cation. ProCharTS is observed profusely among proximal charge clusters in folded proteins. Here, we show that, ProCharTS absorption among growing HBV capsids is amplified when HBV Cp homodimers assemble, generating new contacts among charged residues in the dimer-dimer interface. We notice a time-dependent sigmoidal increase in ProCharTS absorbance and luminescence during capsid formation in comparison to pure dimers. Additionally, a combined approach of anisotropy-based fluorescence assay is reported, where an increased fluorescence anisotropy was observed in capsids as compared to native and unfolded dimers. We conclude that ProCharTS can serve as a sensitive label-free tool for rapid tracking of capsid assembly in real-time and characterize the assembled capsids from dimers.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"6425-6438"},"PeriodicalIF":5.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425668","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":"Detailed Study of the Interactions between Glycopolymers in the Presence of Metal Ions through Quartz Crystal Microbalance Method.","authors":"Tomoya Sumura, Masanori Nagao, Hikaru Matsumoto, Tsukuru Masuda, Madoka Takai, Yoshiko Miura","doi":"10.1021/acs.biomac.4c00493","DOIUrl":"10.1021/acs.biomac.4c00493","url":null,"abstract":"<p><p>Polymer self-assemblies driven by enthalpic interactions, such as hydrogen bonding and electrostatic interactions, exhibit distinct properties compared to those driven by hydrophobic interactions. Carbohydrate-carbohydrate interactions, which are observed in physiological phenomena, also fall under enthalpic interactions. Our group previously reported on self-assemblies of methacrylate-type glycopolymers carrying mannose units in the presence of calcium ions; however, a detailed study of these interactions was lacking. In this work, we investigated the interactions between glycopolymers using the quartz crystal microbalance (QCM) method. Our quantitative analysis revealed that the interactions between the glycopolymers were influenced by the carbohydrate structures in the side chains, the types of divalent metal ions, and the structures of the polymer main chains. Notably, the strongest interaction was observed in the combination of methacrylate-type glycopolymers carrying mannose units and calcium ions, demonstrating their potential as a driving force for polymer self-assembly.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"6416-6424"},"PeriodicalIF":5.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138558","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":"Smart Hydrogel Dressing Enhances the Healing of Chronic Infectious Diabetic Wounds through Dual-Barrier Drug Delivery Action.","authors":"Yaxing Li, Heng Gong, Tingjiang Gan, Xikun Ma, Qirui Geng, Shijiu Yin, Hui Zhang, Ye Wu","doi":"10.1021/acs.biomac.4c01041","DOIUrl":"10.1021/acs.biomac.4c01041","url":null,"abstract":"<p><p>Chronic diabetic wounds struggle to heal due to drug-resistant bacterial infections, oxidative stress microenvironment, and immune dysfunction. At present, the disease has become a huge clinical challenge. Multifunctional hydrogels with antibacterial, antioxidant, and anti-inflammatory properties are becoming an emerging trend in the treatment of chronic wounds. However, matching different bioactive functions with the wound healing process to sequentially exert antibacterial, antioxidant, anti-inflammatory, and immunomodulatory functions remains a significant challenge. In this research, a hydrogel dressing with bactericidal and anti-inflammatory properties was synthesized by crafting a pH/ROS-responsive scaffold from phenylboronic acid-grafted hyaluronic acid (HA-PBA) and 4-arm-PEG-dopamine (4A-PEG-Dopa), employing dynamic borate ester bonds. This structure was then infused with the antimicrobial peptide (AMP) and ROS-sensitive micelle mPEG-TK-PLGA loaded with quercetin (QC). This dressing embodied a dual-barrier drug delivery mechanism, engineered for the prolonged and consistent liberation of QC. In the experiment, the hydrogel dissociated within the acidic microenvironment of diabetic wounds, thereby liberating the encapsulated micelles and AMP. Upon further dissociation, the micelles release QC due to the ROS-abundant microenvironment, which could relieve oxidative stress and encourage M2 polarization of macrophage via the Akt/STAT6 signaling pathway. Therefore, this smart delivery system, developed through our innovative approach, holds promise for treating chronic infectious diabetic wounds.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"6814-6829"},"PeriodicalIF":5.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138559","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}