BiomacromoleculesPub Date : 2025-02-19DOI: 10.1021/acs.biomac.4c01587
Bianka Golba, Zifu Zhong, Matteo Romio, Ruben Almey, Dieter Deforce, Maarten Dhaenens, Niek N Sanders, Edmondo M Benetti, Bruno G De Geest
{"title":"Cyclic Poly(2-methyl-2-oxazoline)-Lipid Conjugates Are Good Alternatives to Poly(ethylene glycol)-Lipids for Lipid Nanopartcile mRNA Formulation.","authors":"Bianka Golba, Zifu Zhong, Matteo Romio, Ruben Almey, Dieter Deforce, Maarten Dhaenens, Niek N Sanders, Edmondo M Benetti, Bruno G De Geest","doi":"10.1021/acs.biomac.4c01587","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01587","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) with ionizable cationic lipids have revolutionized RNA drug delivery, playing a key role in the success of mRNA-based therapeutics, such as COVID-19 vaccines. A vital component of these LNPs is the poly(ethylene glycol) (PEG)-lipid conjugate, which enhances colloidal stability but may trigger the production of anti-PEG antibodies, resulting in accelerated blood clearance (ABC) and diminished therapeutic efficacy. In this study, we explored poly(2-methyl-2-oxazoline) (PMOXA) as an alternative stabilizing agent for mRNA LNPs. We synthesized both cyclic and linear PMOXA, conjugated them to dialkyl lipids, and created lipid-polymer amphiphiles. We systematically evaluated how polymer topology influenced the physicochemical properties of LNPs, including in vitro cellular uptake, transfection efficiency, and protein corona formation, and directly compared these properties with those of PEG-stabilized counterparts. In vivo experiments in mice further assessed the biodistribution and protein translation efficiency of these LNPs following intravenous administration. Our results showed that cyclic PMOXA conjugates not only matched but potentially surpassed the performance of PEG-based analogues, highlighting their promise as a superior alternative in mRNA-LNP formulations.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456266","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 : 2025-02-19DOI: 10.1021/acs.biomac.4c01640
Gege Peng, Guangyao Li, Fei Zhou, Tianlun Shen, Jiali Lyu, Ziyi Liu, Jun Ling, Jihong Sun
{"title":"Bismuth-Loaded Poly(α-amino acid) Nanoparticles for CT and Fluorescence Bimodal Imaging.","authors":"Gege Peng, Guangyao Li, Fei Zhou, Tianlun Shen, Jiali Lyu, Ziyi Liu, Jun Ling, Jihong Sun","doi":"10.1021/acs.biomac.4c01640","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01640","url":null,"abstract":"<p><p>X-ray computed tomography (CT) offers high spatial resolution and deep tissue penetration, but its low sensitivity limits early disease diagnosis. In contrast, fluorescence imaging (FI) provides high sensitivity, suffering from poor spatial resolution and limited tissue penetration. Combining CT and FI creates a complementary imaging method. Herein, we report bismuth-loaded poly(α-amino acid) nanoparticles (abbreviated as Bi NPs including Bi@POS, Bi@POS-FITC, and Bi@POS-ICG) for CT and fluorescence bimodal imaging. Bi NPs exhibit superior X-ray attenuation and fluorescence emission properties by integrating bismuth complexes with fluorescent dyes, including fluorescein isothiocyanate (FITC) and indocyanine green (ICG). The catechol moieties in poly(α-amino acid)s not only chelate Bi<sup>3+</sup> but also exhibit reactive oxygen and nitrogen species (RONS) scavenging activity. <i>In vitro</i> and <i>in vivo</i> experiments demonstrate that Bi NPs have superior bimodal imaging performance, significantly enhanced CT contrast, and prolonged fluorescence signals, suggesting their great potential as bimodal contrast agents for diagnosis applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447438","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 : 2025-02-19DOI: 10.1021/acs.biomac.4c01376
Iyeswaria K Amma, Rohan S J Ingrole, Ghanesh Kesav Venkatesa Prabhu, Raul Dominquez, Dejie Kong, Satish Chandra Hari Mangalara, Gregory B Mckenna, Harvinder Singh Gill
{"title":"Di-Tyrosine Cross-Linking of Elastin-Like Polypeptides through Ruthenium Photoreaction To Form Scaffolds: Fine Tuning Mechanical Properties and Improving Cytocompatibility.","authors":"Iyeswaria K Amma, Rohan S J Ingrole, Ghanesh Kesav Venkatesa Prabhu, Raul Dominquez, Dejie Kong, Satish Chandra Hari Mangalara, Gregory B Mckenna, Harvinder Singh Gill","doi":"10.1021/acs.biomac.4c01376","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01376","url":null,"abstract":"<p><p>Ensuring that the mechanical properties of tissue engineering scaffolds align with those of the target tissues is crucial for their successful integration and functional performance. Tyrosine-tyrosine cross-links are found in nature in numerous proteins including resilin that exhibit enhanced toughness and energy storage capacity. Herein, we investigated the potential of tuning the mechanical properties of scaffolds made from elastin-like polypeptides (ELPs) containing tyrosine residues. Ruthenium-based photoreaction was used to form tyrosine cross-links. To enhance the cytocompatibility of the ELP scaffold, a continuous mode of washing was developed to remove residual ruthenium from the scaffolds. The continuous mode of washing was significantly superior in removing ruthenium and did so in a significantly shorter time as compared to batch washing and the conventional semibatch washing (also called dialysis washing). The range of storage moduli of the fabricated scaffolds spanned tens of Pa to hundreds of kPa. Human fibroblast cells were found to grow in the scaffolds and proliferate. Overall, this work offers a rationale for further developing tyrosine cross-linked ELPs for a broad range of tissue engineering applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447439","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 : 2025-02-18DOI: 10.1021/acs.biomac.4c01621
Keiji Numata
{"title":"The Biology of Natural Polymers Accelerates and Expands the Science of Biomacromolecules: A Focus on Structural Proteins.","authors":"Keiji Numata","doi":"10.1021/acs.biomac.4c01621","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01621","url":null,"abstract":"<p><p>This Perspective explores the use of biomacromolecules in natural materials synthesized by living organisms, such as spider silk, in the development of sustainable synthetic materials. Currently employed synthetic polymers lack the hierarchical complexity and unique properties of natural materials composed of biomacromolecules. By understanding the composition of these natural materials, it may be able to reproduce their properties synthetically. Additionally, research directions involving the use of renewable resources such as nitrogen and carbon dioxide from the air and seawater to develop biomacromolecules such as spider silk and biopolyester via photosynthetic organisms are reviewed. Next-generation biomacromolecule research will aid in the creation of a sustainable global society, advancing fields such as biomanufacturing, agriculture, aquaculture, and other industries.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447441","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 : 2025-02-17DOI: 10.1021/acs.biomac.4c01574
Jianwei Hou, Guobo Chen, Xinghai Hao, Jiali Xu, Geoffrey I N Waterhouse, Zhiming Zhang, Liangmin Yu
{"title":"Coral-Inspired Zinc Acrylate Polymer Utilizing Coumarin as the Fluorescent Unit for Marine Antifouling.","authors":"Jianwei Hou, Guobo Chen, Xinghai Hao, Jiali Xu, Geoffrey I N Waterhouse, Zhiming Zhang, Liangmin Yu","doi":"10.1021/acs.biomac.4c01574","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01574","url":null,"abstract":"<p><p>The need for low-cost and effective antifouling solutions drives innovation in the fields of chemistry, materials science, and biology. In this work, guided by the antifouling strategies used by fluorescent corals, a series of fluorescent zinc acrylate polymer coatings containing coumarin units (ZAR-coumarin) was successfully prepared. The ZAR-coumarin coatings demonstrated excellent antifouling properties due to the synergistic action of multiple antifouling mechanisms, including fluorescent antifouling, natural bactericidal activity, and self-polishing surface renewal (due to ester group (-COO-Zn-OOC-) cleavage). Compared with zinc acrylate coatings without coumarin units (ZAR), the introduction of coumarin units significantly improved the inhibition efficiency for both bacteria and algae. In marine environment tests, the ZAR-AMCO-1, ZAR-ADMCO-1, and ZAR-CAMCO-1 coatings containing optimized amounts of different types of coumarin units maintained good antifouling properties over a 160-day field test period. This research presents an innovative approach to creating marine antifouling coatings.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439380","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 : 2025-02-17DOI: 10.1021/acs.biomac.4c01596
Yujue Wang, Chen Chao, Mingyan Zhang, Cuiping Wang, Huilan Zhu, Jinglin Yu, Les Copeland, Shujun Wang
{"title":"Strategy for Making Starch-Polyphenol Complexes with Multifunctional Properties.","authors":"Yujue Wang, Chen Chao, Mingyan Zhang, Cuiping Wang, Huilan Zhu, Jinglin Yu, Les Copeland, Shujun Wang","doi":"10.1021/acs.biomac.4c01596","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01596","url":null,"abstract":"<p><p>Starch-phenol complexes are of interest due to their potential for health-related functional properties in addition to resistance to enzymic digestion. However, the preparation of such complexes remains a challenge due to the structural features and low solubility of the phenols. The present study sets out a novel protocol to prepare amylose (AM)-polyphenol complexes by forming an AM-lipid complex that incorporates the polyphenol. Three polyphenols (resveratrol, curcumin, and quercetin), which by themselves do not form complexes with AM, were successfully encapsulated by AM through the addition of lauric acid (LA) to form AM-LA-polyphenol complexes. These ternary complexes had a more ordered structure and better functional properties, including antioxidant activity, slower enzymatic digestion, and controlled release of polyphenols, compared with the polyphenols alone or the AM-LA complex. Of the three polyphenols, more curcumin and quercetin were captured through interhelical rather than intrahelical associations. Our study opens up a new way to prepare starch-polyphenol complexes using polyphenols that do not form complexes with AM alone, which will be of great significance for creating novel resistant starches with desirable functionalities.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439282","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 : 2025-02-17DOI: 10.1021/acs.biomac.4c01371
Yu Ikushima, Tatsuya Oshima
{"title":"Development of a Pillar[6]arene Carboxylic Acid Derivative for the Extraction of a Cationic Protein.","authors":"Yu Ikushima, Tatsuya Oshima","doi":"10.1021/acs.biomac.4c01371","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01371","url":null,"abstract":"<p><p>Pillararenes are macrocyclic compounds that can have multiple functional groups and can provide a platform to develop multivalent ligands. Herein, a pillar[6]arene carboxylic acid derivative (OctP[6]CH<sub>2</sub>COOH) was prepared to extract the cationic protein cytochrome c (Cyt-c) into organic solvents. OctP[6]CH<sub>2</sub>COOH was synthesized by the condensation of ethyl 2-(4-octoxyphenoxy) acetate to obtain the pillar[6]arene derivative, followed by alkali hydrolysis. OctP[6]CH<sub>2</sub>COOH showed high extractability for Cyt-c, while a monomer analog and a neutral pillar[6]arene ester derivative did not. The lysine-rich protein Cyt-c was selectively extracted using OctP[6]CH<sub>2</sub>COOH over other cationic proteins because the complexation was a result of the inclusion of the NH<sub>3</sub><sup>+</sup> groups of the lysine residues by the macrocyclic molecule. Cyt-c complexed with OctP[6]CH<sub>2</sub>COOH partially underwent a structural change and exhibited peroxidase activity in organic solvents. This is the first report of protein extraction using pillararene derivatives that can be applied for the separation and modification of proteins.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439381","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":"Material Design, Fabrication Strategies, and the Development of Multifunctional Hydrogel Composites Dressings for Skin Wound Management.","authors":"Ziteng Wu, Dongdong Lu, Shuo Sun, Manqi Cai, Lin Lin, Mingning Zhu","doi":"10.1021/acs.biomac.4c01715","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01715","url":null,"abstract":"<p><p>The skin is fragile, making it very vulnerable to damage and injury. Untreated skin wounds can pose a serious threat to human health. Three-dimensional polymer network hydrogels have broad application prospects in skin wound dressings due to their unique properties and structure. The therapeutic effect of traditional hydrogels is limited, while multifunctional composite hydrogels show greater potential. Multifunctional hydrogels can regulate wound moisture through formula adjustment. Moreover, hydrogels can be combined with bioactive ingredients to improve their performance in wound healing applications. Stimulus-responsive hydrogels can respond specifically to the wound environment and meet the needs of different wound healing stages. This review summarizes the material types, structure, properties, design considerations, and formulation strategies for multifunctional hydrogel composite dressings used in wound healing. We discuss various types of recently developed hydrogel dressings, highlights the importance of tailoring their physicochemical properties, and addresses potential challenges in preparing multifunctional hydrogel wound dressings.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439382","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 : 2025-02-16DOI: 10.1021/acs.biomac.4c01740
Pascal Boucq, Bernard Ucakar, Floriane Debuisson, Raphael Riva, Anne des Rieux, Christine Jérôme, Antoine Debuigne
{"title":"High Internal Phase Emulsion-Templated Hydrophilic Polyphosphoester Scaffolds: Tailoring the Porosity and Degradation for Soft Tissue Engineering.","authors":"Pascal Boucq, Bernard Ucakar, Floriane Debuisson, Raphael Riva, Anne des Rieux, Christine Jérôme, Antoine Debuigne","doi":"10.1021/acs.biomac.4c01740","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01740","url":null,"abstract":"<p><p>Synthetic porous scaffolds are key elements in tissue engineering (TE), requiring controlled porosity for cell colonization, along with a degradation rate aligned with tissue growth. While biodegradable polyester scaffolds are widely used in TE, they are primarily hydrophobic and suited for semirigid to hard tissue applications. This work broadens the scope of TE by introducing porous scaffolds made of polyphosphoesters (PPEs), degradable polymers with adaptable physicochemical properties. PPE hydrogels were shaped into 3D scaffolds using an emulsion templating method, yielding hydrophilic matrices with controlled porosity and tunable Young's moduli for soft tissues. Degradation assays at physiological pH confirmed the scaffolds' biodegradability. Cytotoxicity tests with PPE scaffolds showed excellent cell viability, while RGD functionalization further enhanced cell adhesion. Scaffold colonization, low inflammation, and angiogenesis were demonstrated <i>in vivo</i> through subcutaneous implantation of the scaffolds in mice and histological analysis. These results highlight PPE-based scaffolds as promising candidates for regenerative medicine.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431869","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":"Metallo-Polyampholyte Hydrogel Based on a Y-Shaped Amphoteric Monomer with Robust Antibacterial and Antifouling Performance.","authors":"Qianyi Fang, Jing Yan, Weiwei Wang, Xueting Wang, Jingjie Chen, Yunxin Xu, Xudong Deng, Peng Li, Shixin Fa, Qiuyu Zhang, Yi Yan","doi":"10.1021/acs.biomac.4c01226","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01226","url":null,"abstract":"<p><p>A Y-shaped metallo-amphoteric monomer with cobaltocenium as the cation and sulfonyl as the anion was synthesized and used to prepare the corresponding metallo-polyampholyte hydrogel (PAH). The cobaltocenium in the amphoteric system and its Y-shape may introduce tunable supramolecular interactions, providing regulation of hydration properties and biomedical performance. Such metallo-PAH showed a higher water swelling ratio and comparable mechanical performance in comparison with its organic counterpart, polysulfobetaine methacrylate hydrogel (SBMA-PAH). Moreover, the metallo-PAH showed a good inhibitory effect against Gram-negative bacteria, Gram-positive bacteria, as well as corresponding drug-resistant bacteria. Interestingly, it was found that the metallo-PAH achieved as high as 95% antifouling property against different proteins in both short-term (2 h) and long-term (24 h) tests, which is much better than that of the SBMA-PAH (<50%). It is believed that the concept of \"metallo-polyampholyte\" may expand the field of classical polyampholytes and related materials, thus opening up a new avenue to design powerful antifouling materials.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424620","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}