BiomacromoleculesPub Date : 2025-07-24DOI: 10.1021/acs.biomac.5c00601
Asmita Nandi, Ratan Halder, Diptendu Patra, Afaq Hussain, Subhadeep Roy, Jayasri Das Sarma, Raja Shunmugam
{"title":"Unique Polyester-Based Biodegradable Multiarm Nano-Carrier for Cancer Cell Specific Mitochondrial Delivery of Chemotherapeutics.","authors":"Asmita Nandi, Ratan Halder, Diptendu Patra, Afaq Hussain, Subhadeep Roy, Jayasri Das Sarma, Raja Shunmugam","doi":"10.1021/acs.biomac.5c00601","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00601","url":null,"abstract":"<p><p>Biodegradable polymeric nanocarriers hold significant potential for various biomedical applications, enabling the targeted and controlled delivery of drugs and bioactive molecules. In this context, pendant-functionalized polycaprolactone has garnered tremendous attention over the past few decades. Herein, we developed a mitochondria-targeted polycaprolactone-based polyprodrug, <b>TPP PCL CPT PEG BTN</b>, for the site-specific delivery of camptothecin (CPT). The design incorporates triphenylphosphonium (TPP<sup>+</sup>) and tertiary amine moieties for mitochondrial targeting, biotin (BTN) for receptor-mediated uptake, and CPT as a chemotherapeutic payload. The polymer was synthesized via ring-opening polymerization and alkyne-azide click chemistry and self-assembled into uniform spherical nanoaggregates (∼117 ± 20 nm) as confirmed by DLS, TEM, and SEM. Confocal microscopy demonstrated efficient cellular uptake and mitochondrial localization in HeLa cells. Cytotoxicity assays revealed high selective anticancer activity (IC<sub>50</sub> = 8 μg/mL) with minimal toxicity toward normal HaCaT cells. These findings suggest that <b>TPP PCL CPT PEG BTN</b> is a promising mitochondria-targeted nanocarrier for precision cancer chemotherapy.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697091","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 : 2025-07-23DOI: 10.1021/acs.biomac.5c00795
Sudhanshu Sharma, Jyoti Vishwakarma, Jacek Czub, Subrahmanyam Sappati, Krishna Gavvala
{"title":"Elucidation of the Synergistic Interaction Between Bilirubin and Casein Protein: An Integrated Spectroscopy and Computational Approach.","authors":"Sudhanshu Sharma, Jyoti Vishwakarma, Jacek Czub, Subrahmanyam Sappati, Krishna Gavvala","doi":"10.1021/acs.biomac.5c00795","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00795","url":null,"abstract":"<p><p>Herein, we unveil the interaction between bilirubin (BIL), a liver metabolite, and a milk protein, casein (CAS), through an integrated experimental-computational approach. Encapsulation of BIL within CAS protein micelles was characterized by using UV-vis absorption, steady-state fluorescence, and circular dichroism (CD) spectroscopy. CD analysis revealed conformational modulation of BIL upon encapsulation, accompanied by Förster resonance energy transfer (FRET) from CAS's tryptophans to BIL. <sup>1</sup>H NMR measurements determined specific binding interactions of BIL functional groups involved in micellar interactions, correlating photophysical and electronic properties. The binding affinity of BIL in CAS micelles was found to be on the order of 10<sup>4</sup> M<sup>-1</sup> with a spontaneous binding process (-24.56 kJ/mol) driven by entropy gains (467.17 J/mol). TDDFT calculations unveiled red shifts in BIL's absorption spectra caused by the protein environment. This integrated experimental-computational study provides novel insights into synergetic interactions and structural dynamics between BIL and CAS, shedding light on the influence of milk proteins on bilirubin's behavior.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697089","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":"Lysozyme/Alginate Interactions: Structural and Thermodynamic Insights through ITC and SAXS.","authors":"Asna Vakeri, Antoine Bouchoux, Adeline Boire, Pascaline Hamon, Saïd Bouhallab, Denis Renard","doi":"10.1021/acs.biomac.5c00270","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00270","url":null,"abstract":"<p><p>Coacervation and aggregation are distinct phase separation phenomena influenced by molecular properties and physicochemical conditions, such as pH and ionic strength. We investigate lysozyme (LYS)-alginate (ALG) mixtures at pH 7, focusing on the role of ionic strength in determining whether liquid-liquid phase separation (LLPS) or liquid-solid phase separation (LSPS) occurs. Using Isothermal Titration Calorimetry (ITC) and Small-Angle X-ray Scattering (SAXS), we find that a low salt (0-50 mM NaCl) induces compact fractal aggregates, while the intermediate salt (100-150 mM) yields coexisting or pure coacervates composed of larger swollen primary globules. At 200 mM NaCl, soluble complexes form instead of phase separation. ITC data reveal that both LSPS and LLPS are electrostatically driven, with the binding strength decreasing ∼50-fold from LSPS to LLPS conditions. These results demonstrate that phase behavior is tunable via ionic strength and that stronger interactions correlate with denser structures, highlighting distinct structural and energetic signatures for LSPS and LLPS.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688340","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 : 2025-07-23DOI: 10.1021/acs.biomac.5c00803
Katrin Hommel, Sebastian Theisen, Mike Blueggel, Felix C Niemeyer, Christine Beuck, Peter Bayer, Reza Zadmard, Thomas Schrader, Shirley K Knauer
{"title":"Highly Preorganized Calixarene Tweezers for Protein Recognition.","authors":"Katrin Hommel, Sebastian Theisen, Mike Blueggel, Felix C Niemeyer, Christine Beuck, Peter Bayer, Reza Zadmard, Thomas Schrader, Shirley K Knauer","doi":"10.1021/acs.biomac.5c00803","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00803","url":null,"abstract":"<p><p>Calixarene scaffolds offer structural robustness and tunable geometry for designing selective supramolecular inhibitors. Here, we developed a focused library of preorganized multivalent calix[4]arene tweezers targeting the cancer-related protease Taspase 1. Seven cone-conformation derivatives were synthesized, varying in linker rigidity, functionalization, and multivalency. Meta-dynamics simulations showed that flexible butynyl linkers enabled conformational adaptability, while rigid benzyl linkers promoted structural preorganization. Different biochemical binding assays showed that rigid constructs, particularly the bivalent <b>c2Tl</b> and upper-rim derivatives <b>uc2T</b> and <b>uc4T</b>, most effectively disrupted the Taspase 1/Importin α-interaction by directly binding to the enzyme's loop region near the active site. All constructs inhibited Taspase 1 activity, with <b>c2Tl</b> and <b>uc4T</b> showing the highest potency (low micromolar K<sub>D</sub> values). While polar groups enhanced solubility, they reduced binding affinity; in contrast, increased multivalency and linker rigidity improved inhibition. These results establish rigid, preorganized calix[4]arene ligands as promising scaffolds for targeted enzyme inhibition.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697090","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 : 2025-07-22DOI: 10.1021/acs.biomac.5c00692
Filip Latečka, Tamara Juriňáková, Lukáš Münster, Monika Muchová, Michal Masařík, Anton Kuchynski, Petr Humpolíček, Michaela Fojtů, Jan Vícha
{"title":"Thermoresponsive Hyaluronate-Based Nanogels for Enhanced Phenanthriplatin Delivery in Cisplatin-Resistant Ovarian Cancer.","authors":"Filip Latečka, Tamara Juriňáková, Lukáš Münster, Monika Muchová, Michal Masařík, Anton Kuchynski, Petr Humpolíček, Michaela Fojtů, Jan Vícha","doi":"10.1021/acs.biomac.5c00692","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00692","url":null,"abstract":"<p><p>Stimuli-responsive hyaluronic acid carriers face limitations due to limited carboxyl groups, which are divided between drug conjugation and functional modifications. Thermoresponsive nanogels based on selectively oxidized hyaluronan (2,3-dicarboxy hyaluronate, DCH) grafted with poly(<i>N</i>-isopropyl acrylamide) (pNIPAM) were developed for phenanthriplatin (PhPt) delivery. Sequential oxidation after pNIPAM grafting introduced additional carboxylic groups, enabling a more efficient drug loading and controlled release. Compared to nonoxidized pNIPAM-modified HA, this approach achieved 3 times higher loading efficacy and significantly slower drug release. Upon PhPt loading, DCH-pNIPAM conjugates self-assembled into nanogels, with the drug binding mode (ionic vs covalent) influencing particle rearrangement and drug release behavior. Covalently bound PhPt showed reduced release compared to nonthermoresponsive controls. <i>In vitro</i> studies on ovarian cancer cell lines, including cisplatin-resistant variants, demonstrated up to an 18-fold increase in cytotoxicity versus free PhPt. These nanogels offer a promising strategy for enhancing drug efficacy, reducing off-target effects, and overcoming resistance in cancer therapy.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688343","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 : 2025-07-22DOI: 10.1021/acs.biomac.5c00278
Carina Breuer, Linus Sprandl, Olaf Soltwedel, Regine von Klitzing, Andreas Geissler, Markus Biesalski
{"title":"Understanding and Controlling the Multistep Crystallization of Fatty Acid Cellulose Esters.","authors":"Carina Breuer, Linus Sprandl, Olaf Soltwedel, Regine von Klitzing, Andreas Geissler, Markus Biesalski","doi":"10.1021/acs.biomac.5c00278","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00278","url":null,"abstract":"<p><p>Fatty acid cellulose esters (FACEs) have great potential as biogenic alternatives to petroleum-based plastics. Nevertheless, their thermal property profiles have been the subject of controversial discussion, particularly with respect to their crystallization behavior. A thorough understanding of the crystallization behavior of FACEs is fundamentally important for gaining deep insights into their solid-state characteristics and thermal properties. This systematic study succeeds in elucidating the crystallization behavior of FACEs as bulk materials. Differential scanning calorimetry combined with rheological analysis and X-ray diffraction of cellulose esters bearing side chains with varying numbers of fatty acid residues (C-12-C-20) and degrees of substitution (ranging from partial to full esterification, i.e., 0.1-3.0) revealed that crystallization of FACEs occurs in multiple stages. These stages involve the distinct crystallization of inter and intramolecular side chains and polysaccharide backbones. A quantitative multistep crystallization mechanism is proposed based on the study findings.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688344","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":"Modulation of Photoluminescence To Detect Glutathione-Responsiveness of Phthalimide-Derived Polymeric Micelles.","authors":"Kalipada Manna, Padmapani Pradhan, Subha Samanta, Abhipsa Sekhar Biswal, Santosh Kumar Jana, Sukhendu Mandal, Soumit Chatterjee, Sagar Pal","doi":"10.1021/acs.biomac.5c00331","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00331","url":null,"abstract":"<p><p>The delivery of a drug payload to targeted cells using a polymeric vehicle cannot be accurately traced solely by photoluminescence emission. A multicomponent synthetic method is imperative that should integrate fluorescence change observation along with <i>in vitro</i> release of the therapeutic agent. The present work outlines the design, synthesis, spectroscopic characterization, theoretical approaches, GSH-triggered surface morphology observation, and <i>in vitro</i> release of curcumin from a phthalimide-based pPEGMA<sub>22</sub>-<i>b</i>-pPTHDS<sub>16</sub> copolymer micelle. This copolymer has a disulfide bond as a cleavable linker, a phthalimide group as a fluorescent marker, and curcumin as a model cargo. Disulfide cleavage, initiated by interaction with glutathione under physiological conditions, leads to the liberation of free curcumin and a simultaneous red-shift fluorescence emission (λ<sub>max</sub> = 530 nm). This promising drug delivery system demonstrates potential for theranostic applications for the targeted therapies, as it seamlessly integrates treatment and real-time imaging of drug absorption at a cellular level.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688341","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 : 2025-07-22DOI: 10.1021/acs.biomac.5c00554
Ahmad Ali Saad, Jian-Qiao Jiang, Jesus Raya, Burkhard Bechinger
{"title":"Phosphates Drive the Assembly of Fibers Made from the α-Helical Lentiviral Transduction Enhancer Vectofusin.","authors":"Ahmad Ali Saad, Jian-Qiao Jiang, Jesus Raya, Burkhard Bechinger","doi":"10.1021/acs.biomac.5c00554","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00554","url":null,"abstract":"<p><p>Vectofusin (VF) is a histidine-rich amphipathic peptide designed to enhance lentiviral transduction for gene therapeutic applications, where its assembly into fibrils requires polyvalent anions. In this study, we used solid-state NMR, transmission electron microscopy, and titration experiments to investigate the peptide's phosphate-driven supramolecular assembly. A VF variant lacking two lysines (V2K) was used to further assess the role of charge in these assemblies. Our results show that VF-pyrophosphate self-assembles into ordered, raft-like sheet structures. NMR confirmed that VF-pyrophosphate aggregates maintain an α-helical conformation, with distinct phosphate populations, one of which closely interacts with lysine residues. In contrast, the V2K variant showed weaker pyrophosphate interactions, highlighting the importance of electrostatic contacts in assembly. Based on these findings, we propose a model in which phosphates act as electrostatic glue, linking peptides via their lysine side chains. These insights support the design of new self-assembling biomaterials and improve understanding of phosphate-polypeptide interactions in biological processes.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688342","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":"AIEgen-Based Photoactivatable Polymeric Prodrug Nanoplatform for Combined Photodynamic-Chemotherapy.","authors":"Xiaoqing Yang, Xuehong Min, Xiaoqing Yi, Xinru Nan, Chendi Qin, Chenghao Liu, Ziyue Gong, Linjian Fang, Shijie Zhen, Man Zhou","doi":"10.1021/acs.biomac.5c00763","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00763","url":null,"abstract":"<p><p>The combination of photodynamic therapy (PDT) and chemotherapy is an innovative cancer treatment strategy, but its clinical application faces challenges: (1) conventional photosensitizers exhibit fluorescence quenching and reduced ROS generation due to aggregation in aqueous environments, and (2) existing nanocarriers suffer from low drug loading efficiency, premature leakage, and systemic toxicity. To overcome these issues, we developed a photoactivatable codelivery system integrating a red-emissive AIEgen photosensitizer (BTPTT-NTPE, BC) with a ROS-responsive polymeric paclitaxel (PTX) prodrug. Harnessing the AIE effect, the AIEgen photosensitizer in its aggregated state within the codelivery system not only resolves the fluorescence quenching issue common to conventional photosensitizers but also demonstrates exceptional photostability and efficient ROS generation. The BC@PTP prodrug achieves a high PTX loading (18.0%) and enables spatiotemporally controlled drug release via light-activated prodrug cleavage. This multifunctional system demonstrates remarkable antitumor efficacy through synergistic PDT-chemotherapy effects in a HeLa-bearing mouse animal model.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681666","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 : 2025-07-19DOI: 10.1021/acs.biomac.5c00607
Jiaqian Cui, Junwei Tang, Xijiao Bian, Jungang Jiang, Yifan Zhang, Lei Wang
{"title":"A Lignin-Based Biodegradable Mulch Film with Zn<sup>2+</sup> Coordination Networks for Sustainable Agriculture.","authors":"Jiaqian Cui, Junwei Tang, Xijiao Bian, Jungang Jiang, Yifan Zhang, Lei Wang","doi":"10.1021/acs.biomac.5c00607","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00607","url":null,"abstract":"<p><p>The environmental persistence of conventional plastic mulch films imposes substantial ecological burdens. With rising demands for sustainable agriculture, biodegradable alternatives attract growing interest. However, existing biobased films often face trade-offs between mechanical robustness, environmental adaptability, and functional versatility. In this study, we fabricated a mechanically enhanced multifunctional lignin-based composite mulch by blending modified sulfate lignin (SKL), poly(vinyl alcohol) (PVA), nanocellulose (CNF), and ZnCl<sub>2</sub>. The work elucidated the synergistic interfacial mechanism underlying its superior properties. Zn<sup>2+</sup> coordination with lignin sulfonic acid groups and SKL/PVA/CNF hydrogen bonding form a hierarchical network. This yields exceptional toughness (40.57 MJ/m<sup>3</sup>), ∼99% UV-blocking, hydrophobicity, moisture barrier, and thermal stability. The film degraded 70% in 40 days─far exceeding conventional mulch (CM). Its inherent biodegradability offers significant potential to replace agricultural plastics, advancing sustainable materials.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666641","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}