{"title":"Comparative Study of pH-Responsive and Aggregation Stability of Bosutinib-Loaded Nanogels Comprising Gelatin Methacryloyl, Carboxymethyl Dextran, and Hyaluronic Acid for Controlled Drug Delivery in Colorectal Cancer: An Extensive In Vitro Investigation.","authors":"Sankha Bhattacharya, Shashikant Bagade, Preeti Chidambar Sangave, Devendra Kumar, Imran Shaik, Dhrubojyoti Mukherjee","doi":"10.1021/acs.biomac.4c01209","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01209","url":null,"abstract":"<p><p>This study investigates the use of pH-responsive nanogels for delivering Bosutinib (BOSU) in colon cancer treatment. Nanogels were formulated using three polymers: hyaluronic acid (HA), carboxymethyl dextran (CMD), and gelatin methacryloyl (GelMA). These nanogels achieved high drug entrapment efficiencies (80-90%) through polymer mixing with BOSU, followed by EDC/NHS cross-linking and sonication. The nanogels were stable, with negative zeta potentials (-20 to -30 mV) and particle sizes between 100 and 200 nm. Fourier-transform infrared analysis confirmed successful methacrylation in GelMA nanogels. Sustained BOSU release at pH 5.0 was observed, resembling tumor environments, compared to slower release at normal pH (7.4). Cytotoxicity tests showed 70-80% cell survival reduction in HCT116 colon cancer cells at higher doses, and GelMA-BOSU nanogels notably reduced cell migration. Antiangiogenic effects were confirmed in a chick chorioallantoic membrane model, highlighting the potential of these nanogels for targeted BOSU delivery in colon cancer therapy.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589312","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 : 2024-11-06DOI: 10.1021/acs.biomac.4c01245
Cole A Williams, Daniel J Stone, Soumil Y Joshi, Gokhan Yilmaz, Parisa Farzeen, Sungjin Jeon, Zamira Harris-Ryden, C Remzi Becer, Sanket A Deshmukh, Cassandra E Callmann
{"title":"Systematic Evaluation of Macromolecular Carbohydrate-Lectin Recognition Using Precision Glycopolymers.","authors":"Cole A Williams, Daniel J Stone, Soumil Y Joshi, Gokhan Yilmaz, Parisa Farzeen, Sungjin Jeon, Zamira Harris-Ryden, C Remzi Becer, Sanket A Deshmukh, Cassandra E Callmann","doi":"10.1021/acs.biomac.4c01245","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01245","url":null,"abstract":"<p><p>The precise modulation of protein-carbohydrate interactions is critical in glycobiology, where multivalent binding governs key cellular processes. As such, synthetic glycopolymers are useful for probing these interactions. Herein, we developed precision glycopolymers (PGPs) with unambiguous local chemical composition and well-defined global structure and systematically evaluated the effect of polymer length, hydrophobicity, and backbone hybridization as well as glycan density and identity on the binding to both mammalian and plant lectins. Our studies identified glycan density as a critical factor, with PGPs below 50% grafting density showing significantly weaker lectin interactions. Coarse-grained molecular dynamics simulations suggest that the observed phenomena may be due to a decrease in carbohydrate-carbohydrate interactions in fully grafted PGPs, leading to improved solvent accessibility. In functional assays, these PGPs reduced the cell viability and migration in 4T1 breast cancer cells. Our findings establish a structure-activity relationship in glycopolymers, providing new strategies for designing synthetic glycomacromolecules for a myriad of applications.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581301","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":"Evaluation of the Highly Ordered Structure, Ligature, and Enzymatic Degradation of Poly[(<i>R</i>)-3-hydroxybutyrate-<i>co</i>-4-hydroxybutyrate] Elastic Porous Fibers.","authors":"Sakura Tsujimoto, Taku Omura, Katsuya Komiyama, Taizo Kabe, Akira Maehara, Atsuhiko Murayama, Hitoshi Hirata, Miwa Suzuki, Ken-Ichi Kasuya, Daisuke Takahashi, Tadahisa Iwata","doi":"10.1021/acs.biomac.4c01144","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01144","url":null,"abstract":"<p><p>We prepared biocompatible elastic fibers with high porosity and high tensile strength from poly[(<i>R</i>)-3-hydroxybutyrate-<i>co</i>-4-hydroxybutyrate], which is a microbial polyester that can be produced from renewable carbon resources by isothermal crystallization. It was possible to control the pore size by adjusting the isothermal crystallization time. Most of the pores were approximately less than 10 μm in diameter, did not penetrate, and were distributed discontinuously throughout the fibers. The elasticity of the fibers was apparently attributable to the generation of tie molecules with planar zigzag conformations between lamellar crystals and to the deformation of the pores. The ligature area occupied by the porous fibers in surgical knots was reduced by 75% compared with that of nonporous fibers. This is expected to make the ligature more difficult to untie and reduce the feeling of foreign matter. X-ray tomography revealed that the porous fibers had a relatively small fiber diameter owing to the collapse of the porous area. The rate of enzymatic degradation of the porous fibers was more than four times that of nonporous fibers. These results suggest that this elastic porous fiber will have many applications, including in the medical and marine material fields.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589313","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 : 2024-11-05DOI: 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":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-05","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}
{"title":"Genetically Engineered Liposwitch-Based Nanomaterials.","authors":"Md Shahadat Hossain, Alex Wang, Salma Anika, Zhe Zhang, Davoud Mozhdehi","doi":"10.1021/acs.biomac.4c01388","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01388","url":null,"abstract":"<p><p>Fusion of intrinsically disordered and globular proteins is a powerful strategy to create functional nanomaterials. However, the immutable nature of genetic encoding restricts the dynamic adaptability of nanostructures postexpression. To address this, we envisioned using a myristoyl switch, a protein that combines allostery and post-translational modifications─two strategies that modify protein properties without altering their sequence─to regulate intrinsically disordered protein (IDP)-driven nanoassembly. A typical myristoyl switch, allosterically activated by a stimulus, reveals a sequestered lipid for membrane association. We hypothesize that this conditional exposure of lipids can regulate the assembly of fusion proteins, a concept we term \"liposwitching\". We tested this by fusing recoverin, a calcium-dependent myristoyl switch, with elastin-like polypeptide, a thermoresponsive model IDP. Biophysical analyses confirmed recoverin's myristoyl-switch functionality, while dynamic light scattering and cryo-transmission electron microscopy showed distinct calcium- and lipidation-dependent phase separation and assembly. This study highlights liposwitching as a viable strategy for controlling DP-driven nanoassembly, enabling applications in synthetic biology and cellular engineering.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566661","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 : 2024-11-04DOI: 10.1021/acs.biomac.4c00944
Marika Avitabile, Ana Aleksov, C Valeria L Giosafatto, Odile Francesca Restaino, Marija Lesjak, Nemanja Živanović, Loredana Mariniello, Nataša Simin
{"title":"Pectin-Based Bioplastics Functionalized with Polyphenols from Rose Oil Distillation Wastewater Exhibit Antioxidant Activity.","authors":"Marika Avitabile, Ana Aleksov, C Valeria L Giosafatto, Odile Francesca Restaino, Marija Lesjak, Nemanja Živanović, Loredana Mariniello, Nataša Simin","doi":"10.1021/acs.biomac.4c00944","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c00944","url":null,"abstract":"<p><p>This study explored the potential of rose aqueous extract (RE), a byproduct of rose essential oil extraction, to enhance the properties of biobased food packaging materials. RE contained a high phenolic content (153 mg of GAE/g of dw), rich in hydroxybenzoic acids and flavonols. The antioxidant potential of RE, assessed by DPPH assay, was evaluated (IC<sub>50</sub> = 2.85 μg/mL). Edible pectin films fortified with RE were prepared, and their mechanical, physical, and chemical characteristics were evaluated. RE addition increased the moisture content from 14 to 28%, while moisture uptake remained stable at around 10%. Zeta potential remained below -30 mV, indicating that particle aggregation and particle size decreased with higher RE concentrations. Scanning electron microscopy showed an improved homogeneity of the films. RE retained its antioxidant properties, enhancing the mechanical resistance of the films and offering protection against oxidative damage and UV radiation. These findings suggest the potential of RE in developing functional, eco-friendly food packaging.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566663","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 : 2024-11-02DOI: 10.1021/acs.biomac.4c01149
Yi Ju, Junjie Wang, Yang Lei, Yunbing Wang
{"title":"Powdered Medical Adhesive with Long Lasting Adhesion in Water Environment.","authors":"Yi Ju, Junjie Wang, Yang Lei, Yunbing Wang","doi":"10.1021/acs.biomac.4c01149","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01149","url":null,"abstract":"<p><p>Medical adhesives have been used under surgical conditions. However, it is always a big challenge to maintain long-term adhesion in a water environment. Besides, it usually takes a long time to complete the adhesion, and the operation might be complicated. In this study, tannic acid and gelatin solution under acidic conditions were mixed, flocculated, lyophilized, and crushed; thus, a powdered medical adhesive (POWDER) was prepared with long-lasting adhesion in a water environment, convenience, and low price. Tannic acid bound gelatin and maintained adhesive force primarily through hydrogen bonding and reacted with amino sulfhydryl and other amino acid residues after oxidation into aldehyde, exhibiting excellent underwater adhesion. Oxidized dextran (ODex) powder rich in an aldehyde group was introduced to provide covalent binding in the adhesive. In vitro and in vivo studies showed that POWDER could quickly adhere to various tissues in the water environment. In vitro skin adhesion experiments demonstrated that it could achieve effective adhesion in a water environment for up to 60 days. Its blood compatibility, low cytotoxicity, and biodegradability were also verified. The POWDER developed in this study is of great significance for patients who need rapid wound treatments.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563523","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 : 2024-11-01DOI: 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":"https://doi.org/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":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-01","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 : 2024-11-01DOI: 10.1021/acs.biomac.4c00753
Sheila Bhatt, Peter A. Smethurst, Gil Garnier, Alexander F. Routh
{"title":"Front-Tracking and Gelation in Sessile Droplet Suspensions: What Can They Tell Us about Human Blood?","authors":"Sheila Bhatt, Peter A. Smethurst, Gil Garnier, Alexander F. Routh","doi":"10.1021/acs.biomac.4c00753","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c00753","url":null,"abstract":"Recently developed imaging techniques have been used to examine the redistribution of human red blood cells and comparator particles dispersed in carrier fluids within evaporating droplets. We demonstrate that progressive gelation initiates along an annular front, isolating a central pool that briefly remains open to particulate advection before gelation completes across the droplet center. Transition to an elastic solid is evidenced by cracking initiating proximal to front locations. The arrested flow of cellular components, termed a “halted front”, has been investigated using a time-lapse analysis “signature”. The presence of a deformable biocellular component is seen to be essential for front-halting. We show a dependence of front-halt radius on cell volume-fraction, potentially offering a low-cost means of measuring hematocrit. A simple model yields an estimate of the gel zero-shear yield-stress. This approach to understanding the drying dynamics of blood droplets may lead to a new generation of point-of-care diagnostics.","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"16 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562367","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 Optimization of Ethylenediamine-Based Zwitterion on Polymer Side Chain for Recognizing Narrow Tumorous pH Windows.","authors":"Masahiro Toyoda, Yutaka Miura, Motoaki Kobayashi, Masato Tsuda, Takahiro Nomoto, Yuto Honda, Hiroyuki Nakamura, Hiroyasu Takemoto, Nobuhiro Nishiyama","doi":"10.1021/acs.biomac.4c01086","DOIUrl":"10.1021/acs.biomac.4c01086","url":null,"abstract":"<p><p>Polyzwitterions that show the alternation of net charge in response to external stimuli have attracted great attention as a new class of surface-polymers on nanomedicines. However, the correlation between their detailed molecular structures and expression of antifouling properties under physiological condition remain controversial. Herein, we synthesized a series of ethylenediamine-based polyzwitterions with carboxy groups/sulfonic groups and ethylene, propylene, and butylene spacers as potential surface-polymers for nanomedicines, allowing sensitive recognition of tumor acidic environments (pH = 6.5-5.5). Then, we evaluated their structure-based characteristics, including pH-dependent cellular uptakes and intracellular distributions. Additionally, the role of conformation stability, <i>i.e.</i>, Gibbs free energy changes, was to induce an intramolecular electrostatic interaction in the zwitterionic moieties. These results highlight the practicality of fine-tuning the design of zwitterionic moieties on polymers for the future development of nanomedicines that can recognize the narrow pH window in tumor acidic environments.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556537","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}