BiomacromoleculesPub Date : 2024-12-12DOI: 10.1021/acs.biomac.4c01407
Feng Huang, Jiajie Chen, Xuan Tang, Yujian Li, Haixin Bao, Xuan Mao, Shunqing Tang
{"title":"Preparation and Wound Repair of Injectable and Self-Healing Benzaldehyde-Modified Konjac Glucomannan Oligosaccharide/Polyglutamic Acid/ε-Polylysine Hydrogel.","authors":"Feng Huang, Jiajie Chen, Xuan Tang, Yujian Li, Haixin Bao, Xuan Mao, Shunqing Tang","doi":"10.1021/acs.biomac.4c01407","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01407","url":null,"abstract":"<p><p>Oligosaccharides always have better water solubility, higher possibilities for modification, and unique biofunctions compared with polysaccharides, but they are rarely used as the matrix of a hydrogel. Here, we prepared a composite BKOS/HPGA/PL hydrogel (BKPP hydrogel) constructed by hydrazone/imine bonds between the aldehyde groups of benzaldehyde-modified konjac glucomannan oligosaccharide (BKOS) and the primary amino groups of both hydrazide-modified polyglutamic acid (HPGA) and ε-polylysine (ε-PL). The hydrogels had both injectable and self-healing properties. The gelation time reached 23 s when 2% of BKOS (DS = 21.7%), 10% HPGA (DS = 11.5%), and 10% ε-PL solutions were mixed in a volume ratio of 5:4.5:0.5. Besides high water-retention capability and good cytocompatibility, the hydrogel also maintained both the immunoactivities of BKOS and the antibacterial performances of ε-PL and HPGA, and thus exhibited good wound healing performance in the whole cortex wound repair process of rats, which might have potential for its biomedical application.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816698","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 : 2024-12-11DOI: 10.1021/acs.biomac.4c01282
Anika L Moller, Isis A Middleton, Grace E Maynard, Lachlan B Cox, Anna Wang, Hsiu L Li, Pall Thordarson
{"title":"Discrimination between Purine and Pyrimidine-Rich RNA in Liquid-Liquid Phase-Separated Condensates with Cationic Peptides and the Effect of Artificial Crowding Agents.","authors":"Anika L Moller, Isis A Middleton, Grace E Maynard, Lachlan B Cox, Anna Wang, Hsiu L Li, Pall Thordarson","doi":"10.1021/acs.biomac.4c01282","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01282","url":null,"abstract":"<p><p>Membraneless organelles, often referred to as condensates or coacervates, are liquid-liquid phase-separated systems formed between noncoding RNAs and intrinsically disordered proteins. While the importance of different amino acid residues in short peptide-based condensates has been investigated, the role of the individual nucleobases or the type of heterocyclic structures, the purine vs pyrimidine nucleobases, is less researched. The cell's crowded environment has been mimicked <i>in vitro</i> to demonstrate its ability to induce the formation of condensates, but more research in this area is required, especially with respect to RNA-facilitated phase separation and the properties of the crowding agent, poly(ethylene glycol) (PEG). Herein, we have shown that the nucleotide base sequence of RNA can greatly influence its propensity to undergo phase separation with cationic peptides, with the purine-only RNA decamer <b>(AG)</b><sub><b>5</b></sub> readily doing so while the pyrimidine-only <b>(CU)</b><sub><b>5</b></sub> does not. Furthermore, we show that the presence and size of a PEG macromolecular crowder affects both the ability to phase separate and the stability of coacervates formed, possibly due to co-condensation of PEG with the RNA and peptides. This work sheds light on the presence of low-complexity long purine- or pyrimidine-rich noncomplementary repeat (AG or CU) sequences in various noncoding RNAs found in biology.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811429","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 : 2024-12-11DOI: 10.1021/acs.biomac.4c01061
Anja Traeger, Meike N Leiske
{"title":"<i>The Whole Is Greater than the Sum of Its Parts</i> - Challenges and Perspectives in Polyelectrolytes.","authors":"Anja Traeger, Meike N Leiske","doi":"10.1021/acs.biomac.4c01061","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01061","url":null,"abstract":"<p><p>Polyelectrolytes offer unique properties for biological applications due to their charged nature and high water solubility. Here, the challenges in their synthesis and characterization techniques are reviewed, emphasizing that their strong interactions with the surrounding media and counterions must be considered when working with this interesting class of materials. Their potential in complexation for gene delivery, their unique stealth and anti-fouling properties, and their more specific interactions with amino acid transporters for cancer therapy are highlighted. The underlying mechanisms responsible for their biological efficacy, including the proton sponge effect for endosomal release and their interactions with cellular membranes, are addressed. For polyelectrolytes with a high level of usage, an overview is given of their historical context. This Perspective outlines the potential of polyelectrolytes for innovative applications in the field of biomedicine. Considering the physicochemical characteristics of this class of materials, this work strives to elucidate the distinctive properties and applications of polyelectrolytes.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811428","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 : 2024-12-10DOI: 10.1021/acs.biomac.4c01152
Shangqiang Xie, Congran Yue, Sheng Ye, Zhenlu Li
{"title":"Biological Condensate Growth: Examining the Impact of Solute Crowder on Size Expansion.","authors":"Shangqiang Xie, Congran Yue, Sheng Ye, Zhenlu Li","doi":"10.1021/acs.biomac.4c01152","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01152","url":null,"abstract":"<p><p>Biological condensation refers to the formation of micrometer-sized or smaller condensates by biological macromolecules, a process often influenced by the crowded cellular environment. Poly(ethylene glycol) (PEG) is commonly used to mimic cellular crowding, and its ability to reduce the critical nucleation concentration has been well established. However, its impact on condensate size has been less explored. This study investigates how PEG affects the size of condensates formed between protein TNP1 and DNA. Our experimental findings show that PEG molecules increase condensate size. Notably, at equal mass concentrations of PEG400, PEG3350, and PEG10000, longer PEG molecules have a much greater effect on condensate expansion. Computational simulations further reveal that longer PEG molecules enhance protein-DNA condensation more effectively and contribute to shaping the condensates into regular forms. Overall, our study provides key insights into how crowding factors influence the size and shape of colloidal growth.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798630","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 : 2024-12-09Epub Date: 2024-11-01DOI: 10.1021/acs.biomac.4c00985
Gayatri Prakash, Aaron J Clasky, Kunal Gadani, Mohammad Nazeri, Frank X Gu
{"title":"Ion-Mediated Cross-Linking of Hyaluronic Acid into Hydrogels without Chemical Modification.","authors":"Gayatri Prakash, Aaron J Clasky, Kunal Gadani, Mohammad Nazeri, Frank X Gu","doi":"10.1021/acs.biomac.4c00985","DOIUrl":"10.1021/acs.biomac.4c00985","url":null,"abstract":"<p><p>Hyaluronic acid (HA) is a biomedically relevant polymer widely explored as a component of hydrogels. The prevailing approaches for cross-linking HA into hydrogels require chemically modifying the polymer, which can increase processing steps and complicate biocompatibility. Herein, we demonstrate an alternative approach to cross-link HA that eliminates the need for chemical modifications by leveraging the interactions between metal cations and the negatively charged, ionizable functional groups on HA. We demonstrate that HA can be cross-linked with the bivalent metal cations Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), and notably Mg(II). Using Mg(II) as a model, we show that ion-HA hydrogel rheological properties can be tuned by altering the HA molecular weight and concentrations of ions, NaOH, and HA. Mg(II)-HA hydrogels showed the potential for self-healing and stimulus response. Our findings lay the groundwork for developing a new class of HA-based hydrogels for use in biomedical applications and beyond.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"7723-7735"},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562384","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 : 2024-12-09DOI: 10.1021/acs.biomac.4c01250
Manseok Yang, Sujin Kim, Seungwon Jeong, Suyeon Lee, Seunga Lee, Hanui Jo, Nuri Kim, Nanhee Song, Seong-Cheol Park, Dongwon Lee
{"title":"Harnessing Dual-Responsive Polymeric Micelles for Precision Oxidative Stress Amplification in Targeted Cancer Therapy.","authors":"Manseok Yang, Sujin Kim, Seungwon Jeong, Suyeon Lee, Seunga Lee, Hanui Jo, Nuri Kim, Nanhee Song, Seong-Cheol Park, Dongwon Lee","doi":"10.1021/acs.biomac.4c01250","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01250","url":null,"abstract":"<p><p>Targeting the altered redox balance in cancer cells, this study explores a strategy to induce selective cancer cell death by combining reactive oxygen species (ROS) generation with glutathione (GSH) depletion. We developed oxidative stress-amplifying polymeric (pCB) micelles that function both as therapeutic agents and carriers for GSH-depleting retinoic acid prodrug (BRDP). pCB incorporating ROS-generating cinnamaldehyde and a GSH-depleting quinone methide precursor could self-assemble into micelles encapsulating BRDP, delivering both ROS generators and GSH-depleting drugs. The micelles were surface-functionalized with the tripeptide Arg-Gly-Asp (RGD) for targeted delivery to integrin-overexpressing tumors. In a mouse xenograft model, RGD-decorated BRDP-loaded micelles significantly accumulated in tumor sites, enhancing anticancer efficacy without toxicity to normal tissues. This study marks significant advancement in the field of oxidative stress-amplifying polymeric precursors, presenting a novel and highly effective anticancer therapeutic approach that integrates multiple tumor-specific triggers and ROS-mediated mechanisms.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794031","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 : 2024-12-09Epub Date: 2024-11-05DOI: 10.1021/acs.biomac.4c01192
Tianren Zhang, Dai-Bei Yang, Christopher J Kloxin, Darrin J Pochan, Jeffery G Saven
{"title":"Coarse-Grain Model of Ultrarigid Polymer Rods Comprising Bifunctionally Linked Peptide Bundlemers.","authors":"Tianren Zhang, Dai-Bei Yang, Christopher J Kloxin, Darrin J Pochan, Jeffery G Saven","doi":"10.1021/acs.biomac.4c01192","DOIUrl":"10.1021/acs.biomac.4c01192","url":null,"abstract":"<p><p>Computationally designed homotetrameric helical peptide bundles have been functionalized at their N-termini to achieve supramolecular polymers, wherein individual bundles (\"bundlemers\") are the monomeric units. Adjacent bundles are linked via two covalent cross-links. The polymers exhibit a range of conformational properties, including formation of rigid-rods with micrometer-scale persistence lengths. Herein, a coarse-grained model is used to illuminate how molecular features affect the rod-like behavior of the polymers. With increasing affinity between bundlemer ends, a sharp transition in the persistence length is observed. Doubly linked chains exhibit larger persistence lengths and more robust formation of rigid-rod structures than singly linked chains. Chain stiffness increases with decreasing temperatures. Increasing the length of the cross-linker results in more flexible chains. This model provides insights into how molecular features control the structural properties of chains comprising doubly linked rigid bundlemers.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"7904-7914"},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581157","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 : 2024-12-09Epub Date: 2024-11-08DOI: 10.1021/acs.biomac.4c01099
Rafał Jerzy Kopiasz, Maciej Dranka, Waldemar Tomaszewski, Patrycja Kowalska, Beata Butruk-Raszeja, Karolina Drężek, Jolanta Mierzejewska, Tomasz Ciach, Dominik Jańczewski
{"title":"Antimicrobial Macrocycles - Synthesis, Characterization, and Activity Comparison with Their Linear Polycationic Analogues.","authors":"Rafał Jerzy Kopiasz, Maciej Dranka, Waldemar Tomaszewski, Patrycja Kowalska, Beata Butruk-Raszeja, Karolina Drężek, Jolanta Mierzejewska, Tomasz Ciach, Dominik Jańczewski","doi":"10.1021/acs.biomac.4c01099","DOIUrl":"10.1021/acs.biomac.4c01099","url":null,"abstract":"<p><p>One of the promising candidates for new antimicrobial agents is membrane-lytic compounds that kill microbes through cell membrane permeabilization, such as antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs). Although SMAMPs have been under investigation for nearly 30 years, a few challenges must be addressed before they can reach clinical use. In this work, a step-growth polymerization leading to already-known highly antimicrobial ionenes was redirected toward the formation of macrocyclic quaternary ammonium salts (MQAs) employing a high dilution principle. Antimicrobial assays and cytotoxicity studies revealed the high antimicrobial activity of MQAs and better selectivity than their polymeric analogues. Therefore, MQAs seem to be a new class of promising antibacterial agents. Additionally, membrane-lytic experiments using large unilamellar liposomes (LUVs) and whole cells revealed significant differences between MQAs and ionenes in their ability to adsorb onto the surface of LUVs and microbes as well as their ability to permeate the lipid bilayer.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"7814-7827"},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602373","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 : 2024-12-09Epub Date: 2024-11-08DOI: 10.1021/acs.biomac.4c01128
Ping Wei, Kai Chen, Jinghua Chen
{"title":"Engineering an Ultrasound-Responsive Glycopolymersome for Hepatocyte-Specific Gene Delivery.","authors":"Ping Wei, Kai Chen, Jinghua Chen","doi":"10.1021/acs.biomac.4c01128","DOIUrl":"10.1021/acs.biomac.4c01128","url":null,"abstract":"<p><p>The ability to design liver-targeted gene delivery vectors is plagued with difficulties ranging from carrier-mediated cellular toxicity to challenges in encapsulating sensitive nucleic acids. Herein, we present an ultrasound-responsive glycopolymersome strategy for <i>in situ</i> loading of nucleic acids and achieving hepatocyte-specific gene delivery. This glycopolymersome is self-assembled from a block copolymer, <i>N</i>-acetylgalactosamine-grafted poly(glutamic acid)-<i>block</i>-poly(ε-caprolactone) (PGAGalNAc-<i>b</i>-PCL). GalNAc is introduced to afford liver targeting through the selective binding to the asialoglycoprotein receptor overexpressed on hepatocytes. External ultrasound is utilized to assist in encapsulating nucleic acids within the hydrophilic lumen of glycopolymersomes by exploiting their ultrasound responsiveness nature. Biological studies confirmed the successful encapsulation of plasmid DNA (pDNA) and small interfering RNA (siRNA), rapid nuclear internalization, and efficient gene transfection. These findings collectively demonstrated that this ultrasound-responsive glycopolymersome could be exploited as a novel safe and efficient gene vector targeting hepatocytes.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"7838-7849"},"PeriodicalIF":5.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602387","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}