Materials Today Bio最新文献

{"title":"Extracellular vesicles from human adipose-derived stem cell spheroids: Characterization and therapeutic implications in diabetic wound healing","authors":"Edgar Daniel Quiñones ,&nbsp;Mu-Hui Wang ,&nbsp;Kuan-Ting Liu ,&nbsp;Ting-Yu Lu ,&nbsp;Guan-Yu Lan ,&nbsp;Yu-Ting Lin ,&nbsp;Yu-Liang Chen ,&nbsp;Tang-Long Shen ,&nbsp;Pei-Hsun Wu ,&nbsp;Yu-Sheng Hsiao ,&nbsp;Er-Yuan Chuang ,&nbsp;Jiashing Yu ,&nbsp;Nai-Chen Cheng","doi":"10.1016/j.mtbio.2024.101333","DOIUrl":"10.1016/j.mtbio.2024.101333","url":null,"abstract":"<div><div>The management of diabetic wounds presents a considerable challenge within the realm of clinical practice. Cellular-derived nanoparticles, or extracellular vesicles (EV), generated by human adipose-derived stem cells (hASCs) have been investigated as promising candidates for the treatment of diabetic wounds. Nevertheless, limitations on the yield, as well as the qualitative angiogenic properties of the EV produced, have been a persistent issue. In this study, a novel approach involving the use of various cell culture morphologies, such as cell spheroids, on hASC was used to promote both EV yield and qualitative angiogenic properties for clinical use, with an emphasis on the in vivo angiogenic properties exhibited by the EV. Moreover, an increase in the secretion of the EV was confirmed after cell spheroid culture. Furthermore, microRNA(miRNA) analysis of the produced EVs indicated an increase in the presence of wound healing-associated miRNAs on the cell spheroid EV. Analysis of the effectiveness of the treated EVs in vitro indicated a significant promotion of the biological function of fibroblast and endothelial cells, cell migration, and cell proliferation post-cell spheroid EV application. Meanwhile, in vivo experiments on diabetic rats indicated a significant increase in collagen production, re-epithelization, and angiogenesis of the diabetic wound after EV administration. In this investigation, we posit that the use of cell spheroids for the culture of hASC represents a novel approach to enhance the substantial secretion of extracellular vesicles while increasing the angiogenic wound healing properties. This innovation holds promise for augmenting the therapeutic potential of EVs in diabetic wound healing, aligning with the exigencies of clinical applications for these nanoparticles.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101333"},"PeriodicalIF":8.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered biomimetic nanovesicles-laden multifunctional hydrogel enhances targeted therapy of diabetic wound","authors":"Shuoyuan Liu ,&nbsp;Gui Wan ,&nbsp;Tao Jiang ,&nbsp;Chengqi Yan ,&nbsp;Guoyong Jiang ,&nbsp;Maojie Zhang ,&nbsp;Kaituo Xiang ,&nbsp;Chi Zhang ,&nbsp;Xuejiao Xiang ,&nbsp;Huayuan Zhao ,&nbsp;Chengcheng Li ,&nbsp;Zhichao Ruan ,&nbsp;Yangyang Chen ,&nbsp;Yanhua Chen ,&nbsp;Xiaofan Yang ,&nbsp;Zhenbing Chen","doi":"10.1016/j.mtbio.2024.101330","DOIUrl":"10.1016/j.mtbio.2024.101330","url":null,"abstract":"<div><div>Angiogenesis is essential for diabetic wound healing. Endothelial progenitor cell-derived extracellular vesicles (EPC-EVs) are known to promote wound healing by enhancing angiogenesis, while the low yield and lack of effective targeting strategies limit their therapeutic efficacy. Here, the biomimetic nanovesicles (NVs) prepared from EPC (EPC-NV) through an extrusion approach were reported, which functioned as EV mimetics to deliver contents from EPC to the wound. Besides, the cRGD peptide was coupled to the surface of EPC-NV (mEPC-NV) to achieve active endothelial cells (ECs)-targeting. Furthermore, we developed a dual hydrogel network by combining Fe³⁺@ Protocatechualdehyde (PA) complex-modified Acellular Dermal Matrix (ADM) with light-cured gelatin (GelMA), to enrich and sustainably release mEPC-NV. The hydrogel system with antioxidant and antibacterial properties also made up for the deficiency of mEPC-NV, reducing reactive oxygen species (ROS) and inhibiting infection in diabetic wound. Taken together, this study established a novel bioactive delivery system with angiogenesis, antioxidant and antibacterial activities, which might be a promising strategy for the treatment of diabetic wound.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101330"},"PeriodicalIF":8.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel-based cardiac patches for myocardial infarction therapy: Recent advances and challenges","authors":"Zhenqiu Liu ,&nbsp;Zhi Zheng ,&nbsp;Jiahao Xie ,&nbsp;Hua Wei ,&nbsp;Cui-Yun Yu","doi":"10.1016/j.mtbio.2024.101331","DOIUrl":"10.1016/j.mtbio.2024.101331","url":null,"abstract":"<div><div>Myocardial infarction (MI) remains the leading cause of death related to cardiovascular diseases globally, presenting a significant clinical challenge due to the specificity of the lesion site and the limited proliferative capacity of cardiomyocytes (CMs) for repairing the infarcted myocardium. Extensive studies reported so far has focused on the utilization of hydrogel-based cardiac patches for MI treatment, highlighting their promising mechanical properties, conductivity, and ability to remodel the microenvironment post-repair. However, the majority of developed cardiac patches have been limited to the myocardial tissue surface via suturing or adhesive administration. Suturing inevitably leads to additional damage to the fragile myocardium, while uneven application of adhesives may result in patch displacement and compromised drug release. Based on these critical issues, we systematically summarize the advantages and drawbacks of using hydrogel patches for MI treatment with emphasis on elucidating various design strategies. Specifically, we first describe the changes in the pathological microenvironment following MI. Next, we discuss the biomimetic types of hydrogel patches, their functional design, and corresponding strategies for microenvironment adaptation, emphasizing adhesion mechanisms, wet adhesion design strategies, and fabrication techniques for hydrogel patches. Finally, we address the potential challenges and prospects of hydrogels as patches for MI therapy. The review is believed to provide theoretical guidance for the development of new therapeutic strategies for effectively MI treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101331"},"PeriodicalIF":8.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“On-demand” nanosystem-integrated microneedles for amplified triple therapy against recalcitrant bacteria and biofilm growth","authors":"Ting Wen ,&nbsp;Yiting Zhao ,&nbsp;Yanping Fu ,&nbsp;Ying Chen ,&nbsp;Xiaodie Li ,&nbsp;Chaonan Shi ,&nbsp;Dongyi Xian ,&nbsp;Wanchen Zhao ,&nbsp;Dan Yang ,&nbsp;Chao Lu ,&nbsp;Chuanbin Wu ,&nbsp;Xin Pan ,&nbsp;Guilan Quan","doi":"10.1016/j.mtbio.2024.101327","DOIUrl":"10.1016/j.mtbio.2024.101327","url":null,"abstract":"<div><div>Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes could reduce bacterial tolerance, a multifunctional “on-demand” nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant <em>Staphylococcus aureus</em> (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection. After MNs insertion, the nanoplatform could specifically deliver the loaded therapeutic components to bacterial infection sites through employing hyaluronic acid (HA) as a capping agent, thus realizing the “on-demand” payload release triggered by excess hyaluronidase secreted by MRSA. The prepared nanosystem and MNs were confirmed to exert an amplified triple therapy originating from membranolytic effect, phototherapy, and ion therapy, thus displaying a powerful bactericidal and MRSA biofilm destruction ability. This intelligent antimicrobial strategy may bring a dawn of hope for eradicating multidrug-resistant bacteria and biofilms.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101327"},"PeriodicalIF":8.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switchable ROS generator and scavenger to prevent the cisplatin induced acute kidney injury and improve efficacy via synergistic chemodynamic/immune therapy","authors":"Yanan Ren ,&nbsp;Fei Wu ,&nbsp;Linlin Huo ,&nbsp;Xiao Wang ,&nbsp;Yong Zhang ,&nbsp;Mengke Fan ,&nbsp;Mingya Tan ,&nbsp;Jiayi Zhao ,&nbsp;Jingliang Cheng ,&nbsp;Zhenghuan Zhao ,&nbsp;Jianfeng Bao","doi":"10.1016/j.mtbio.2024.101328","DOIUrl":"10.1016/j.mtbio.2024.101328","url":null,"abstract":"<div><div>Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall Mn₃O₄ nanozyme (UMON) with tumor microenvironment (TME) responsive ROS scavenging and generating as adjuvant to alleviate DDP induced AKI with improved efficacy. In kidney, UMON with superoxide dismutase and catalase activity acts as ROS scavenger to eliminate ROS generated by DDP, successfully protecting the renal cells/tissue and alleviating AKI during DDP treatment. Alternatively, UMON rapidly responses to the high GSH level in TME and release Mn²⁺ in tumor. This unique feature endows it to generate hydroxyl radicals (∙OH) through a Fenton-like reaction and deplete GSH in tumor cell and tissue, achieving high efficient chemodynamic therapy (CDT). More importantly, the Mn²⁺ successfully activates the cGAS-STING pathway, initiating the immune response and effectively inhibiting the tumor metastases. The synergistic CDT and immune therapy effectively improve the anti-tumor efficacy of DDP <em>in vitro</em> and <em>in vivo</em>. This study demonstrates that TME responsive ROS scavenger/generator shows the potential to reduce side effects of DDP while improve its therapeutic efficacy, providing a new avenue to achieve efficient chemotherapy and promoting the progress of clinical chemotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101328"},"PeriodicalIF":8.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An AIE fungal vacuole membrane probe toward species differentiation, vacuole formation visualization, and targeted photodynamic therapy","authors":"Bingnan Wang ,&nbsp;Siyuan Wang ,&nbsp;Chunyang Li ,&nbsp;Jianqing Li ,&nbsp;Meixi Yi ,&nbsp;Jing-Wen Lyu ,&nbsp;Bing Gu ,&nbsp;Ryan T.K. Kwok ,&nbsp;Jacky W.Y. Lam ,&nbsp;Anjun Qin ,&nbsp;Ben Zhong Tang","doi":"10.1016/j.mtbio.2024.101329","DOIUrl":"10.1016/j.mtbio.2024.101329","url":null,"abstract":"<div><div>Vacuoles are unique organelles of fungi. The development of probes targeting the vacuoles membrane will enable visualization of physiological processes and precise diagnosis and therapy. Herein, a zwitterionic molecule, MXF-R, comprising of an aggregation-induced emission (AIE) photosensitizing unit and an antibiotic moxifloxacin, was found capable of specifically imaging vacuole membrane and using for targeted antifungal therapy. MXF-R demonstrated a higher signal-to-noise ratio, stronger targeting capability, and better biocompatibility than the commercial probe FM4-64. By using MXF-R, real-time visualization of vacuole formation during <em>Candida albicans</em> (<em>C. albicans</em>) proliferation was achieved. More importantly, owing to its varying staining ability towards different fungus, MXF-R could be used to quickly identify <em>C. albicans</em> in mixed strains by fluorescence imaging. Moreover, MXF-R exhibits a remarkable ability to generate reactive oxygen species under white light, effectively eradicating <em>C. albicans</em> by disrupting membrane structure. This antifungal therapy of membrane damage is more effective than clinical drug fluconazole. Therefore, this work not only presents the initial discovery of a probe targeting vacuolar membrane, but also provides a way to develop novel materials to realize integrated diagnosis and therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101329"},"PeriodicalIF":8.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical confinement matters: Unveiling the effect of two-photon polymerized 2.5D and 3D microarchitectures on neuronal YAP expression and neurite outgrowth","authors":"Ahmed Sharaf ,&nbsp;Jean-Philippe Frimat ,&nbsp;Angelo Accardo","doi":"10.1016/j.mtbio.2024.101325","DOIUrl":"10.1016/j.mtbio.2024.101325","url":null,"abstract":"<div><div>The effect of mechanical cues on cellular behaviour has been reported in multiple studies so far, and a specific aspect of interest is the role of mechanotransductive proteins in neuronal development. Among these, yes-associated protein (YAP) is responsible for multiple functions in neuronal development such as neuronal progenitor cells migration and differentiation while myocardin-related transcription factor A (MRTFA) facilitates neurite outgrowth and axonal pathfinding. Both proteins have indirectly intertwined fates via their signalling pathways. There is little literature investigating the roles of YAP and MRTFA <em>in vitro</em> concerning neurite outgrowth in mechanically confined microenvironments. Moreover, our understanding of their relationship in immature neurons cultured within engineered confined microenvironments is still lacking. In this study, we fabricated, via two-photon polymerization (2PP), 2.5D microgrooves and 3D polymeric microchannels, with a diameter range from 5 to 30 μm. We cultured SH-SY5Y cells and differentiated them into immature neuron-like cells on both 2.5D and 3D microstructures to investigate the effect of mechanical confinement on cell morphology and protein expression. In 2.5D microgrooves, both YAP and MRTFA nuclear/cytoplasmic (N/C) ratios exhibited maxima in the 10 μm grooves indicating a strong relation with mechanical-stress-inducing confinement. In 3D microchannels, both proteins’ N/C ratio exhibited minima in presence of 5 or 10 μm channels, a behaviour that was opposite to the ones observed in the 2.5D microgrooves and that indicates how the geometry and mechanical confinement of 3D microenvironments are unique compared to 2.5D ones due to focal adhesion, actin, and nuclear polarization. Further, especially in presence of 2.5D microgrooves, cells featured an inversely proportional relationship between YAP N/C ratio and the average neurite length. Finally, we also cultured human induced pluripotent stem cells (hiPSCs) and differentiated them into cortical neurons on the microstructures for up to 2 weeks. Interestingly, YAP and MRTFA N/C ratios also showed a maximum around the 10 μm 2.5D microgrooves, indicating the physiological relevance of our study. Our results elucidate the possible differences induced by 2.5D and 3D confining microenvironments in neuronal development and paves the way for understanding the intricate interplay between mechanotransductive proteins and their effect on neural cell fate within engineered cell microenvironments.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101325"},"PeriodicalIF":8.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro- and nano-fibers for organ-on-a-chip: Construction, applications, and prospects","authors":"Xiaoling Yang ,&nbsp;Jingyan Shi ,&nbsp;Bori Shi ,&nbsp;Jianing Li ,&nbsp;Chang Xue ,&nbsp;Jingyun Ma ,&nbsp;Xinghua Gao","doi":"10.1016/j.mtbio.2024.101322","DOIUrl":"10.1016/j.mtbio.2024.101322","url":null,"abstract":"<div><div>Organ-on-a-chip, an in vitro biomimetic microsystem that enables precise regulation and real-time observation of the cell microenvironment, has the potential to become a powerful platform for recapitulating the real microenvironment of organs in vitro. Microenvironmental factors, such as living cells, three-dimensional (3D) culture, tissue–tissue interfaces, and biomechanical factors, are important cues in the construction of biomimetic microsystems. It is important to provide an appropriate 3D culture environment for living cells to grow. Fibers, particularly microfibers and nanofibers, can provide a suitable 3D culture environment for living cells via surface adhesion or internal loading. In addition, fibers can further expand their applications in tissue engineering and biomedical research by being assembled at a higher level in various ways to create functional 3D tissues or organs with more complex structures. The use of fiber to construct an organ-on-a-chip, whether as a 3D scaffold for cell culture or to more closely mimic real tissues/organs, will introduce new ideas and strategies for developing novel organ-on-a-chip systems. Based on this context, this review summarizes the research progress in the construction and applications of micro/nanofibers for organ-on-a-chip systems. It outlines the preparation methods and material selections for micro/nanofibers and provides a detailed overview of their respective strategies for cell 3D culture and organ-on-a-chip construction. This review also highlights the main research findings and applications of micro/nanofiber in this field, which have significant implications for future practice, and finally concludes by examining potential directions for future development.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101322"},"PeriodicalIF":8.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional hydrogel based on polyvinyl alcohol/chitosan/metal polyphenols for facilitating acute and infected wound healing","authors":"Ruigang Zhou ,&nbsp;Junjie Huang ,&nbsp;Wenhai Zhang ,&nbsp;Weimei Wang ,&nbsp;Weilong Peng ,&nbsp;Jun Chen ,&nbsp;Chenglong Yu ,&nbsp;Ruonan Bo ,&nbsp;Mingjiang Liu ,&nbsp;Jingui Li","doi":"10.1016/j.mtbio.2024.101315","DOIUrl":"10.1016/j.mtbio.2024.101315","url":null,"abstract":"<div><div>Bacterial-infected wounds could cause delayed wound healing due to increased inflammation, especially wounds infected by drug-resistant bacteria remain a major clinical problem. However, traditional treatment strategies were gradually losing efficacy, such as the abuse of antibiotics leading to enhanced bacterial resistance. Therefore, there was an urgent need to develop an antibiotic-free multifunctional dressing for bacterially infected wound healing. This study demonstrated the preparation of a multifunctional injectable hydrogel and evaluated its efficacy in treating acute and infected wounds. The hydrogel was prepared by a one-step mixing method, and cross-linked by natural deep eutectic solvent (DES), polyvinyl alcohol (PVA), chitosan (CS), tannic acid (TA), and Cu²⁺ through non-covalent interactions (hydrogen bonds and metal coordination bonds). PVA/CS/DES/CuTA₅₀₀ hydrogel has multiple functional properties, including injectability, tissue adhesion, biocompatibility, hemostasis, broad-spectrum antibacterial, anti-inflammatory, and angiogenesis. Most importantly, in the <em>MRSA</em>-infected skin wound model, PVA/CS/DES/CuTA₅₀₀ hydrogel could ultimately accelerate infected wound healing by killing bacteria, activating M2 polarization, inhibiting inflammation, and promoting angiogenesis. In summary, the PVA/CS/DES/CuTA₅₀₀ hydrogel showed great potential as a wound dressing for bacterial infected wounds treatment in the clinic.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101315"},"PeriodicalIF":8.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer","authors":"Enyew Alemayehu Bayle ,&nbsp;Fasih Bintang Ilhami ,&nbsp;Jem-Kun Chen ,&nbsp;Chih-Chia Cheng","doi":"10.1016/j.mtbio.2024.101319","DOIUrl":"10.1016/j.mtbio.2024.101319","url":null,"abstract":"<div><div>We combined carbon dioxide (CO₂)-responsive cytosine-containing rhodamine 6G (Cy-R6G) as a hydrophobic anticancer agent with hydrogen-bonded cytosine-functionalized polyethylene glycol (Cy-PEG) as a hydrophilic supramolecular carrier to construct a CO₂-responsive drug delivery system, with the aim of enhancing the responsiveness of the system to the tumor microenvironment and thus the overall effectiveness of anticancer therapy. Due to self-complementary hydrogen bonding interactions between cytosine units, Cy-R6G and Cy-PEG co-assemble in water to form spherical-like nanogels, with Cy-R6G effectively encapsulated within the nanogels. The nanogels exhibit several distinctive physical features, such as widely tunable nanogel size and drug loading capacity for Cy-R6G, intriguing fluorescence properties, high co-assembled structural stability in normal aqueous environments, enhanced anti-hemolytic characteristics, sensitive dual CO₂/pH-responsive behavior, and precise and easily controllable CO₂-induced release of Cy-R6G. Cytotoxicity assays clearly indicated that, due to the presence of cytosine receptors on the surface of cancer cells, Cy-R6G-loaded nanogels exert selective cytotoxicity against cancer cells in pristine culture medium, but do not affect the viability of normal cells. Surprisingly, in CO₂-rich culture medium, Cy-R6G-loaded nanogels exhibit a further significant enhancement in cytotoxicity against cancer cells, and remain non-cytotoxic to normal cells. More importantly, a series of <em>in vitro</em> experiments demonstrated that compared to pristine culture medium, CO₂-rich culture medium promotes more rapid selective internalization of Cy-R6G-loaded nanogels into cancer cells through cytosine-mediated macropinocytosis and thus accelerates the induction of apoptosis. Therefore, this newly developed system provides novel avenues for the development of highly effective CO₂-responsive drug delivery systems with potent anticancer capabilities.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101319"},"PeriodicalIF":8.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}