BiomacromoleculesPub Date : 2025-01-28DOI: 10.1021/acs.biomac.4c01473
Ling-Kun Zhang, Li Liu, Ziqing Li, Yiquan Zhang, Limin Zhai, Luna Zhang, Chu-Hua Li, Yan-Qing Guan
{"title":"Polyphenylalanine-Baicalein Nanomicelles Reduce Nerve Cell Apoptosis and Inflammation to Enhance Neuroprotection and Poststroke Rehabilitation.","authors":"Ling-Kun Zhang, Li Liu, Ziqing Li, Yiquan Zhang, Limin Zhai, Luna Zhang, Chu-Hua Li, Yan-Qing Guan","doi":"10.1021/acs.biomac.4c01473","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01473","url":null,"abstract":"<p><p>Cerebral ischemic stroke, neuronal death, and inflammation bring difficulties in neuroprotection and rehabilitation. In this study, we developed and designed the ability of natural lactoferrin-polyethylene glycol-polyphenylalanine-baicalein nanomicelles (LF-PEG-PPhe-Bai) to target and reduce these pathological processes, such as neurological damage and cognitive impairment in the stages of poststroke. Nanomicelles made from biocompatible materials have improved bioavailability and targeted distribution to afflicted brain areas. The results showed that LF-PEG-PPhe-Bai greatly improved the antioxidation, antiapoptosis, and anti-inflammation activity <i>in vitro</i>. Meanwhile, LF-PEG-PPhe-Bai improved the behavioral and cognitive impairment of 2-VO model mice, protected nerve cells in the hippocampus, and reduced inflammation at the brain injury site <i>in vivo</i>. In conclusion, LF-PEG-PPhe-Bai nanomicelles are employed for enhancing neuroprotection and poststroke rehabilitation. The development of this technology might provide a new technique for neural repair after ischemia in the future.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057539","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":"Synthesis and Characterization of Lipid-Polyzwitterion Diblock Copolymers for Optimizing Micelle Formation to Enhance Anticancer Drug Delivery in 2D and 3D Cell Cultures.","authors":"Chitinart Thedrattanawong, Miao Zhang, Zhongxing Zhang, Xia Song, Jingling Zhu, Xuehao Tian, Jun Li, Yuting Wen","doi":"10.1021/acs.biomac.4c01370","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01370","url":null,"abstract":"<p><p>Amphiphilic polymers with distinct polarity differences, known as sharp polarity contrast polymers (SPCPs), have gained much attention for their ability to form micelles with low critical micelle concentrations (CMCs) and potential in anticancer drug delivery. This study addresses the limited research on structure-property relationships of SPCPs by developing various SPCPs and exploring their physicochemical properties and biological applications. Specifically, the superhydrophobic aliphatic palmitoyl (Pal) was coupled to the superhydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) to form Pal-pMPC diblock copolymers. Adjusting the lengths of hydrophilic chains allowed the creation of structures with varying hydrophilic-hydrophobic ratios for micelle formation. Comprehensive evaluations were carried out, including particle size, CMC, chain exchange rates, cellular uptake efficiency, and anticancer effectiveness. Our findings indicate that micelles with optimal hydrophilic-hydrophobic ratios significantly enhanced cellular uptake and cytotoxicity in both two-dimensional (2D) and three-dimensional (3D) tumor models, offering valuable insights for designing SPCPs for anticancer drug delivery.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050961","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 : 2025-01-26DOI: 10.1021/acs.biomac.4c01410
Hyo Jae Jeon, Joo Hyung Lee, Ae Ji Park, Jeong-Mo Choi, Kyungtae Kang
{"title":"A Single Amino Acid Model for Hydrophobically Driven Liquid-Liquid Phase Separation.","authors":"Hyo Jae Jeon, Joo Hyung Lee, Ae Ji Park, Jeong-Mo Choi, Kyungtae Kang","doi":"10.1021/acs.biomac.4c01410","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01410","url":null,"abstract":"<p><p>This study proposes fluorenylmethoxycarbonyl (Fmoc)-protected single amino acids (Fmoc-AAs) as a minimalistic model system to investigate liquid-liquid phase separation (LLPS) and the elusive liquid-to-solid transition of condensates. We demonstrated that Fmoc-AAs exhibit LLPS depending on the pH and ionic strength, primarily driven by hydrophobic interactions. Systematic examination of the conditions under which each Fmoc-AA undergoes LLPS revealed distinct residue-dependent trends in the critical concentrations and phase behavior. Importantly, we elucidated the liquid-to-solid transition process, suggesting that it may be driven by a molecular mechanism different from that of LLPS. Fmoc-AA condensates showed promise for biomolecular enrichment and catalytic applications. This work provides significant insights into the molecular mechanisms of LLPS and the subsequent liquid-to-solid transition, offering a robust platform for future studies related to protocells and protein aggregation diseases.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044912","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 : 2025-01-26DOI: 10.1021/acs.biomac.4c01080
Yuqing Liu, Wen Zhong, Yongfeng Ai, Malcolm Xing
{"title":"Double Cross-linked Methacrylated Carboxymethyl Pea Starch Cryogels with Highly Compressive Elasticity and Hemostatic Function.","authors":"Yuqing Liu, Wen Zhong, Yongfeng Ai, Malcolm Xing","doi":"10.1021/acs.biomac.4c01080","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01080","url":null,"abstract":"<p><p>As an abundant renewable natural material, starch has attracted unprecedented interest in the biomedical field. Carboxylated starch particles have been investigated for topical hemostasis, but the powder may not provide physical protection or support for wounds. Here, we prepared macroporous cryogel sponges of methacrylated carboxymethyl starch (CM-ST-MA) containing a covalent and a calcium ionic double network. The second ionic cross-linking network enhanced the compressive strength and toughness dramatically but reduced the swelling ratios. Cryogels and sponges exhibited excellent compressive elasticity at low Ca<sup>2+</sup> concentrations (0.01 M). Cryogels became more plastic and dry sponges became rigid and brittle at high Ca<sup>2+</sup> concentrations. The cryogels have outstanding wet-thermal stability but are still degradable via enzymatic hydrolysis. All CM-ST-MA sponges showed excellent biocompatibility, hemocompatibility, and outstanding hemostasis in in vitro assays. In the in vivo mouse tail amputation model, both CM-ST-MA cryogels without or with Ca<sup>2+</sup> (0.01 M) reduced the blood loss and bleeding time significantly.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044925","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 : 2025-01-24DOI: 10.1021/acs.biomac.4c01550
Yichun Yuan, Sophia Beilharz, Heather R Everson, Nehal Nupnar, Mithun Kumar Debnath, Daniele Vinella, Juan Manuel Urueña, Faruk H Örge, Michael J A Hore, Divita Mathur, Metin Karayilan
{"title":"Injectable Fluorescent Bottlebrush Polymers for Interventional Procedures and Biomedical Imaging.","authors":"Yichun Yuan, Sophia Beilharz, Heather R Everson, Nehal Nupnar, Mithun Kumar Debnath, Daniele Vinella, Juan Manuel Urueña, Faruk H Örge, Michael J A Hore, Divita Mathur, Metin Karayilan","doi":"10.1021/acs.biomac.4c01550","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01550","url":null,"abstract":"<p><p>Injectable biomaterials play a vital role in modern medicine, offering tailored functionalities for diverse therapeutic and diagnostic applications. In ophthalmology, for instance, viscoelastic materials are crucial for procedures such as cataract surgery but often leave residues, increasing postoperative risks. This study introduces injectable fluorescent viscoelastics (FluoVs) synthesized via one-step controlled radical copolymerization of oligo(ethylene glycol) acrylate and fluorescein acrylate. These bottlebrush-shaped polymers exhibit enhanced fluorescence intensity for improved traceability and facile removal postsurgery. To prevent aggregation, charged terpolymers were synthesized, ensuring intra- and intermolecular electrostatic repulsion. Dynamic light scattering and energy-conserved dissipative particle dynamics simulations revealed how the fluorescein content and monomer sequence affect the hydrodynamic size of these copolymers. Biocompatibility assessments showed that FluoVs maintained cell viability comparable to commercial hydroxypropyl methylcellulose and nonfluorescent poly(oligo(ethylene glycol) acrylate) controls. The FluoVs combine high fluorescence intensity, low viscosity, and excellent biocompatibility, offering intraoperative traceability and significant advancements for ocular and bioimaging applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027450","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 : 2025-01-23DOI: 10.1021/acs.biomac.4c01515
Han Jia, Mulan Mu, Yangzhe Hou, Yamin Pan, Chuntai Liu, Changyu Shen, Xianhu Liu
{"title":"Template-Thermally Induced Phase Separation-Assisted Microporous Regulation in Poly(lactic acid) Aerogel for Sustainable Radiative Cooling.","authors":"Han Jia, Mulan Mu, Yangzhe Hou, Yamin Pan, Chuntai Liu, Changyu Shen, Xianhu Liu","doi":"10.1021/acs.biomac.4c01515","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01515","url":null,"abstract":"<p><p>Herein, an eco-friendly and degradable poly(lactic acid) aerogel was prepared by combining a poly(ethylene glycol) template material with thermally induced phase separation. Due to the tailored pore size introduced by the template material, the aerogel exhibits high solar reflectance (92.0%), excellent thermal emittance (90.5%), low thermal conductivity (52.0 mW m<sup>-1</sup> K<sup>-1</sup>), and high compressive strength (0.15 MPa). Cooling tests demonstrate that the aerogel can achieve temperature drops of 3.7 °C during the day and of 6.2 °C at night. Furthermore, simulations of building cooling energy systems reveal that the aerogel can reduce energy consumption by 2.2 to 10.2 MJ m<sup>-2</sup> per year in various cities, achieving energy savings ranging from 8.2 to 24.3%. Meanwhile, the aerogel cooler demonstrates excellent self-cleaning performance (WCA = 149.1°) and cyclic compression performance. This research will promote the field of passive radiative cooling toward a greener and more sustainable direction.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021305","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 : 2025-01-23DOI: 10.1021/acs.biomac.4c01634
Hongyan Wang, Lin Shi, Zhongxu Zhang, Long Chen, Xinli Xu, Weiwei Ding, Chuntao Chen, Dongping Sun
{"title":"Fructose-Modified Chitosan/Gelatin 3D Composite Sponge for Enhanced Rapid Hemostasis.","authors":"Hongyan Wang, Lin Shi, Zhongxu Zhang, Long Chen, Xinli Xu, Weiwei Ding, Chuntao Chen, Dongping Sun","doi":"10.1021/acs.biomac.4c01634","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01634","url":null,"abstract":"<p><p>Managing uncontrolled and noncompressible bleeding presents a major challenge in emergency trauma care. Methods to halt bleeding quickly and efficiently, without applying direct pressure on the wound, have become a key focus of research. Herein, a novel fructose-modified chitosan/gelatin composite sponge has been developed, exhibiting high elasticity, low rebound pressure, and excellent cell compatibility. This material can rapidly return to its original form in around 1.5 s after being compressed by 80% upon contact with water. Additionally, experimental results from a rat liver wound model demonstrated that it exhibited a clear hemostatic effect. The hemostatic time was shortened from 204 ± 15.35 s to 53.3 ± 6.54 s, and the blood loss was reduced from 867 ± 153.15 mg to 187 ± 61.06 mg. Moreover, it can promote tissue healing by inhibiting the production of inflammatory factors including TNF-α, MCP-1, and IL-6. This material offers an effective solution for noncompressible tissue injuries.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027436","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 : 2025-01-23DOI: 10.1021/acs.biomac.4c01519
Harrison Laurent, David J Brockwell, Lorna Dougan
{"title":"Nanomachine Networks: Functional All-Enzyme Hydrogels from Photochemical Cross-Linking of Glucose Oxidase.","authors":"Harrison Laurent, David J Brockwell, Lorna Dougan","doi":"10.1021/acs.biomac.4c01519","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01519","url":null,"abstract":"<p><p>Enzymes are attractive as catalysts due to their specificity and biocompatibility; however, their use in industrial and biomedical applications is limited by stability. Here, we present a facile approach for enzyme immobilization within \"all-enzyme\" hydrogels by forming photochemical covalent cross-links between the enzyme glucose oxidase. We demonstrate that the mechanical properties of the enzyme hydrogel can be tuned with enzyme concentration and the data suggests that the dimeric nature of glucose oxidase results in unusual gel formation behavior which suggests a degree of forced induced dimer dissociation and unfolding. We confirm and quantify the enzyme activity of the hydrogel using the Trinder assay and a 1D modeling approach and show that 50% enzymatic activity is retained upon hydrogel formation. These observed effects may be due to the forces experienced by the individual nanoscale enzymes during mesoscale network formation. We have therefore demonstrated that photochemical cross-linking can be readily employed to produce functional all-enzyme glucose oxidase hydrogels with easily tunable mechanical properties and specific catalytic activity. This approach provides enormous potential for producing biocatalytic materials with tunable mechanical properties, responsive biological functionality and high volumetric productivity which may inform the future design of biomedical devices with enhanced sensitivity and activity.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027452","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 : 2025-01-23DOI: 10.1021/acs.biomac.4c01411
David Koam, Ha Yeon Park, Dong Sun Kim, Hyeong Jin Kwon, Yan Lee, Kyobum Kim, Mitsuru Naito, Hyun Jin Kim
{"title":"Amphiphilic Polyaspartamide Derivatives with Cholesterol Introduction Enhanced Ex Vivo mRNA Transfection Efficiency to Natural Killer Cells.","authors":"David Koam, Ha Yeon Park, Dong Sun Kim, Hyeong Jin Kwon, Yan Lee, Kyobum Kim, Mitsuru Naito, Hyun Jin Kim","doi":"10.1021/acs.biomac.4c01411","DOIUrl":"10.1021/acs.biomac.4c01411","url":null,"abstract":"<p><p>Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its <i>ex vivo</i> delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the α-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the <i>ex vivo</i> engineering of NK cells.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027435","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 : 2025-01-22DOI: 10.1021/acs.biomac.4c01441
Han Nguyen, Ngoc Ha Luong, Jacqueline K Peil, Yan Tong, Dana K Mitchell, Melissa L Fishel, Chien-Chi Lin
{"title":"Fast-Relaxing Hydrogels Promote Pancreatic Adenocarcinoma Cell Aggressiveness through Integrin β1 Signaling.","authors":"Han Nguyen, Ngoc Ha Luong, Jacqueline K Peil, Yan Tong, Dana K Mitchell, Melissa L Fishel, Chien-Chi Lin","doi":"10.1021/acs.biomac.4c01441","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01441","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) exhibiting high stiffness and fast stress relaxation. In this work, gelatin-based viscoelastic hydrogels were developed to mimic the compositions, stiffness, and fast stress relaxation of PDAC tissues. The hydrogels were cross-linked by gelatin-norbornene-boronic acid (GelNB-BA), thiolated macromers, and a 1,2-diol-containing linear synthetic polymer PHD. Controlling the thiol-norbornene cross-linking afforded tunable stiffness, whereas increasing PHD content led to hydrogels with PDAC-mimicking fast stress relaxation. <i>In vitro</i> studies, including proliferation, morphology, and mRNA-sequencing, showed that fast-relaxing hydrogels supported PDAC cell proliferation, epithelial-mesenchymal transition (EMT), and integrin β1 activation. Blocking integrin β1 <i>in vitro</i> led to upregulating EMT markers in both slow and fast-relaxing hydrogels. However, this strategy profoundly impacted tumor growth rate and reduced tumor size but did not alter metastasis patterns in an orthotopic mouse model. This suggests a need to further evaluate the antitumor effect of integrin β1 blockade.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021303","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}