Materials Today Bio最新文献

{"title":"Multifunctional nanotherapeutics reprogramming the immunopathological landscape for rheumatoid arthritis therapy","authors":"Anping Shen ,&nbsp;Xiangshu Cheng ,&nbsp;Yuelong Cao ,&nbsp;Hongping Deng","doi":"10.1016/j.mtbio.2025.102379","DOIUrl":"10.1016/j.mtbio.2025.102379","url":null,"abstract":"<div><div>As a prototypical and highly prevalent form of autoimmune disease, rheumatoid arthritis (RA) serves as a valuable model for elucidating pathogenic mechanisms and developing targeted and functional nanomedicines. Emerging research not only offers promising alternatives for RA patients that are incompatible with conventional disease-modifying antirheumatic drugs (DMARDs), but also inspires the engineering of innovative nanomedicines via interdisciplinary science and technology. This review presents a comprehensive overview of the immunopathological landscape of RA, emphasizing the key players in disease development and progression, including fibroblast-like synoviocyte, macrophage, lymphocyte and neutrophil, and delineates how these pathogenic processes create opportunities for targeted intervention. We highlight cutting-edge advances in microneedle-enhanced transdermal delivery, intelligent polymeric biomimetic targeting systems and multifunctional composite platforms. Furthermore, we explore critical developmental pathways for potential clinical translation by employing precision targeting strategies, advancing co-delivery technologies and integrating diagnostics with therapeutics. Collectively, these perspectives offer significant insights for refining precision treatment paradigms in RA.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102379"},"PeriodicalIF":10.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating superlubricative nanomaterials with precision drug delivery for advanced osteoarthritis therapy","authors":"Xin Gan ,&nbsp;Jianwen Li ,&nbsp;Song Li ,&nbsp;Xiaohui Wang ,&nbsp;Qianqiu Wang ,&nbsp;Xin Chen ,&nbsp;Yiwan Huang ,&nbsp;Mingbo Nie ,&nbsp;Hao Kang ,&nbsp;Heshuang Dai","doi":"10.1016/j.mtbio.2025.102359","DOIUrl":"10.1016/j.mtbio.2025.102359","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disorder characterized by chronic inflammation, impaired lubrication, and progressive cartilage degradation. To address these multifaceted pathologies, we developed a multifunctional nanoparticle, termed HPQ@K, based on hyaluronic acid (HA), for co-delivery of quercetin (QUT) — a compound with anti-inflammatory, antioxidant, and hyaluronidase properties — and kartogenin (KGN), which induces chondroautophagy and cartilage regeneration. QUT was conjugated to HA through reactive oxygen species (ROS)- and pH-sensitive boronate ester linkages, leading to self-assembled micelles that encapsulate KGN and enable stimulus-responsive drug release under inflammatory OA conditions. HPQ@K retains the innate lubricity and biocompatibility of HA, while exhibiting enhanced resistance to enzymatic degradation, thereby prolonging its joint residence time. Its nanospheric structure ensures uniform articular coverage and combines hydration lubrication with a \"ball-bearing\" effect to achieve superlubricity. In murine chondrocytes, OA models, and human cartilage tissues, HPQ@K enhanced drug bioavailability and enabled spatiotemporally controlled release, mitigating oxidative stress, restoring mitochondrial function, promoting autophagy, and reducing cellular senescence. Furthermore, it significantly lowered friction coefficients and protected cartilage from mechanical damage. Collectively, HPQ@K constitutes an all-in-one nanotherapeutic platform that concurrently targets inflammation, restores joint lubrication, and facilitates cartilage repair, offering a comprehensive triple-therapy strategy for advanced OA.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102359"},"PeriodicalIF":10.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective targeting of coagulation factor X Gla domain by negatively charged gold nanoparticles: a novel method for controlled antithrombotic therapy","authors":"Shixin Li ,&nbsp;Yuye Yin ,&nbsp;Dongmei Hou ,&nbsp;Yongchao Jin ,&nbsp;Yuan Zhao ,&nbsp;Jiangbo Tong ,&nbsp;Xu Liu ,&nbsp;Guomin Shen ,&nbsp;Tongtao Yue ,&nbsp;Kang Liu ,&nbsp;Yi Gu ,&nbsp;Luju Chen ,&nbsp;Fangzhe Ren ,&nbsp;Jinlin Huang ,&nbsp;Jian-Ke Tie ,&nbsp;Zhenyu Hao","doi":"10.1016/j.mtbio.2025.102378","DOIUrl":"10.1016/j.mtbio.2025.102378","url":null,"abstract":"<div><div>Venous thromboembolism (VTE) presents a significant global health burden due to its high incidence and potentially life-threatening complications. Although anticoagulants targeting vitamin K-dependent (VKD) factors, particularly factor X (FX), are widely employed, their efficacy is often limited by bleeding risks arising from off-target effects. Nanoparticle-based strategies, by contrast, enable precise and tunable modulation of protein activity through controlled adjustments in particle size, charge, and functionalization. In this work, we engineered negatively charged gold nanoparticles (GNPs) of defined sizes to selectively interact with the γ-carboxyglutamic acid (Gla) domain of VKD coagulation proteins. Using computational simulations, we systematically compared their binding conformations and affinities between GNPs and diverse VKD coagulation proteins, uncovering a size-dependent binding mechanism. This finding was subsequently validated through biochemical assays at both the molecular and cellular levels. Notably, GNPs with diameters of 2–3 nm demonstrated significantly higher affinity for FX compared to other VKD proteins, such as factor IX and protein C. This specific binding triggered substantial conformational changes in FX, diminishing its membrane-binding affinity. These structural alterations also reduced its enzymatic activity and impaired its activation efficiency within the coagulation cascade, thereby effectively attenuating the cascade by selectively modulating FX activity. Comprehensive <em>in vitro</em> coagulation assays and <em>in vivo</em> murine thrombosis models further validated that GNP treatment effectively prolonged coagulation time, demonstrating robust antithrombotic efficacy. Collectively, our results establish a novel nanoparticle-based therapeutic paradigm for targeting FX, offering an innovative and promising approach for enhancing the safety and efficacy of VTE prevention and management.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102378"},"PeriodicalIF":10.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional modelling of lymphangiogenesis in-vitro using bioorthogonal click-crosslinked gelatin hydrogels","authors":"Dana E. Al-Ansari ,&nbsp;Yangshuo Hu ,&nbsp;Nicola Contessi Negrini ,&nbsp;Daisy Jones ,&nbsp;Graeme M. Birdsey ,&nbsp;Adam D. Celiz","doi":"10.1016/j.mtbio.2025.102367","DOIUrl":"10.1016/j.mtbio.2025.102367","url":null,"abstract":"<div><div>Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vessels, is crucial for maintaining tissue homeostasis and immune function. Despite recent advances in understanding the molecular mechanisms regulating lymphangiogenesis, most <em>in vitro</em> studies rely on traditional two-dimensional (2D) cell cultures, with limited replication of the complex microenvironment that governs lymphangiogenesis <em>in vivo</em>. Here, we present a three-dimensional (3D) lymphangiogenesis model using gelatin hydrogels modified with click-chemistry motifs (tetrazine and norbornene, GelTN), providing a biomimetic and mechanically tunable extracellular matrix (ECM) for lymphatic endothelial cells. By encapsulating human dermal lymphatic endothelial cells (HDLEC) spheroids in GelTN, we established a robust and reliable <em>in vitro</em> sprouting assay (&lt;48 h duration) to investigate the effects of GelTN stiffness on lymphangiogenesis. HDLEC encapsulated in low GelTN concentrations exhibited enhanced sprouting in response to vascular endothelial growth factor (VEGF)-C stimulation, compared to HDLEC encapsulated in higher GelTN concentrations. We also provide evidence for the involvement of β3 integrin in lymphangiogenesis. The reduced sprout length upon β3 integrin inhibition further decreased with combined inhibition of α5β1, suggesting a synergistic interaction of the integrin subunits in controlling HDLEC-ECM mechanotransduction. GelTN hydrogels were also evaluated for their translational potential, demonstrating sustained release of VEGF-C <em>in vitro</em> and supporting cellular infiltration and neo-vessel formation following subcutaneous injection in an <em>in vivo</em> mouse model. Overall, these findings highlight the versatility of GelTN hydrogels as a platform for studying lymphangiogenesis and their potential use for therapeutic applications that require controlled growth factor delivery in tissue engineering and regenerative medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102367"},"PeriodicalIF":10.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the role of polyethylene glycol coating in reducing the subcellular toxicity of MXene nanoparticles using a large multimodal model","authors":"Aditya Yadav ,&nbsp;Eugene Lee ,&nbsp;Rui Chen ,&nbsp;Soryong R. Chae ,&nbsp;Yujie Sun ,&nbsp;Jiajie Diao","doi":"10.1016/j.mtbio.2025.102372","DOIUrl":"10.1016/j.mtbio.2025.102372","url":null,"abstract":"<div><div>MXenes exhibit remarkable properties such as high electrical conductivity, mechanical strength, and versatile surface chemistry, positioning them as promising candidates for various applications in energy storage, biomedical engineering, and environmental remediation. However, concerns regarding their potential toxicity necessitate a deeper understanding of their interactions with biological systems. This study investigates the subcellular interactions of MXenes, focusing on the mitochondria, endoplasmic reticulum (ER), and lysosomes. Using structured illumination microscopy (SIM), the observations reveal that MXenes exhibit selective toxicity, primarily causing structural damage to the ER, while leaving mitochondria and lysosomes largely unaffected. This organelle-specific toxicity appears to be linked to the negative surface charge of MXenes, which modulates their interactions with cellular components. Notably, surface modification of MXenes with polyethylene glycol (PEG) significantly reduces ER toxicity, thereby improving biocompatibility and offering a promising strategy for safer biomedical applications. Building on these findings, it also introduces a novel methodology that employs a large multimodal model (LMM), a state-of-the-art artificial intelligence (AI) framework, for the automated analysis and interpretation of super-resolution microscopy images.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102372"},"PeriodicalIF":10.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Top-down and Bottom-up” cholesterol-depleting biomimetic nanoparticle for enhancing sonodynamic therapy against hepatocellular carcinoma","authors":"Meng Yang ,&nbsp;Weizhuang Chen ,&nbsp;Junru Zhou ,&nbsp;Fangxia Guan ,&nbsp;Ruimei Jin","doi":"10.1016/j.mtbio.2025.102370","DOIUrl":"10.1016/j.mtbio.2025.102370","url":null,"abstract":"<div><div>Cholesterol depletion in tumor cells has been demonstrated as an effective strategy for cancer therapy. Previous studies have shown that cholesterol oxidase (COD) could promote cholesterol consumption. However, these tumor cells typically upregulate cholesterol synthesis as a compensatory mechanism to meet the rapid proliferation demands. To address this issue, we synthesized HM/ZIF-8@COD/IR820 nanoparticle, which simultaneously facilitates cholesterol depletion and inhibits cholesterol synthesis to enhance sonodynamic therapy against hepatocellular carcinoma (HCC). This HM/ZIF-8@COD/IR820 biomimetic nanoparticle was constructed by encapsulating cholesterol oxidase (COD) and the sonosensitizer indocyanine green (IR820) into ZIF-8 nanoparticle, followed by coating with a hybrid cell membrane from tumor cells and erythrocyte membrane. The hybrid membrane provides tumor-targeting capability, enabling HM/ZIF-8@COD/IR820 nanoparticle homes to Hepa1-6 tumor and disassembles in response to the acidic microenvironment and ultrasound stimulation. In vitro and in vivo studies confirmed significant cholesterol depletion and alleviation of hypoxia in Hepa1-6 cells. Upon ultrasound activation, a significant amount of reactive oxygen species (ROS) was generated, thereby enhancing the therapeutic effect on the inoculated tumors. Non-targeted metabolomics analysis further validated the downregulation of cholesterol metabolism-related pathways, which was consistent with the Filipin staining results observed in cellular experiments. Importantly, Hepa1-6 tumor growth was significantly suppressed and the inhibition rate reached 90%. These findings highlight HM/ZIF-8@COD/IR820 as a promising biomimetic nanoparticle orchestrates a two-pronged attack on hepatocellular carcinoma cholesterol metabolism: top-down suppression of cholesterol biosynthetic pathways, and bottom-up elimination of existing cholesterol stores, yielding outstanding therapeutic effects against HCC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102370"},"PeriodicalIF":10.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted S100A8 PP-Cas9@PLGA-apt microparticles reduced cartilage degradation and subchondral bone isomerism in osteoarthritis treatment through JAK/STAT3 pathway modulation","authors":"Zhong Chen ,&nbsp;Miaomiao Zhou ,&nbsp;Jialong Luo ,&nbsp;Changchuan Li ,&nbsp;Shixun Li ,&nbsp;Sipeng Lin ,&nbsp;Xinghao Deng ,&nbsp;KeLong Zhu ,&nbsp;Yue Ding","doi":"10.1016/j.mtbio.2025.102354","DOIUrl":"10.1016/j.mtbio.2025.102354","url":null,"abstract":"<div><div>Synovial inflammation caused by osteoarthritis (OA) results in the release of numerous pro-inflammatory factors that promote cartilage degradation and pathological changes of subchondral bone. Nowadays, S100A8 has been recognized as a critical factor in the progression of inflammatory diseases, but its role in OA still needs to be confirmed. At the same time, the gene editing technology has emerged as a novel therapeutic approach for OA, such as clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, but application in inflammatory gene therapy still requires advanced delivery systems to ensure cell-specific targeting and biosafety.</div><div>In this study, S100A8 was confirmed as a key mediator perpetuating JAK/STAT3 pathway activation in OA progression by integrated RNA bioinformatics and synovial proteomic analyses. Based on it, we developed a polyamidoamine (PAMAM)-poly (lactic-co-glycolic acid) (PLGA) (PP) nanocore electrostatically complexed with Cas9-S100A8, encapsulated within an aptamer (apt)-grafted PLGA shell structure. This multifunctional nanocarrier could reduce dendrimer toxicity to cells and protein degradation, and enhance cellular targeting and endocytic capacity. PP-Cas9-S100A8@PLGA-apt exhibited 64.4 % S100A8 knockout efficiency (p &lt; 0.001) and sustained mRNA release (71.5 % retention at 48 h), high cell viability (&gt;80 %), and synovium-specific uptake (98.8 % at 0.8 μg/mL), inhibiting the JAK/STAT3 pathway. In OA-induced mice, this inhibition reduced pro-inflammatory responses, cartilage degradation, and attenuated osteophyte volume.</div><div>Our findings first established PP-Cas9-S100A8@PLGA-apt as an efficient and safe Cas9 delivery tool, advancing studies of JAK/STAT3 pathway inhibition and the clinical translation of gene therapy for OA.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102354"},"PeriodicalIF":10.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smart biomaterials in restorative dentistry: Recent advances and future perspectives","authors":"Jianpeng Sun ,&nbsp;Jingang Jiang ,&nbsp;Zhiyuan Huang ,&nbsp;Xuefeng Ma ,&nbsp;Tao Shen ,&nbsp;Jie Pan ,&nbsp;Zhuming Bi","doi":"10.1016/j.mtbio.2025.102349","DOIUrl":"10.1016/j.mtbio.2025.102349","url":null,"abstract":"<div><div>Smart biomaterials in restorative dentistry are engineered to detect and respond to diverse physiological and environmental stimuli, including mechanical stress, pH fluctuations, temperature changes, and magnetic or electrical fields. Unlike conventional inert restorative materials, these intelligent systems integrate both diagnostic and therapeutic functions into clinical practice. This review systematically summarizes recent advances in smart restorative materials using a methodology that combines literature-based classification with comparative evaluation. The materials are categorized into nanocomposites, hydrogels, bioactive agents, chemical and resin-based systems, intelligent carrier platforms, and ceramic-based materials. For each category, we examine design strategies, underlying mechanisms, and representative experimental or preclinical findings. The analysis highlights progress in drug delivery, antibacterial–remineralization coupling, self-healing capacity, and tissue engineering applications. In addition, the review outlines the advantages and limitations of each material class, evaluates their readiness for clinical translation, and identifies technical barriers to widespread adoption. Finally, future research directions are discussed, including multi-stimulus coupling, bioinspired functionalization, and integration with digital dentistry technologies. Overall, this review provides a comprehensive methodological and developmental perspective on smart restorative materials, with the goal of supporting their translation from laboratory innovation to clinical application.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102349"},"PeriodicalIF":10.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual–magnetically driven nanozymes for glioblastoma immunotherapy via magnetothermal and NIR–amplified ferroptosis and apoptosis","authors":"Hui Liu ,&nbsp;Xiaochuan Yang ,&nbsp;Xianwen Liang ,&nbsp;Ying Xia","doi":"10.1016/j.mtbio.2025.102363","DOIUrl":"10.1016/j.mtbio.2025.102363","url":null,"abstract":"<div><div>The hindrance posed by the blood-brain barrier (BBB) and the unique characteristics of the tumor microenvironment (TME) remain major challenges in glioblastoma (GBM) therapy. Here, we developed a dual-magnetically driven ultrasmall Mo_0.2Fe_2.8O₄@CeO_x/FA (MFCF) nanozyme exhibiting multienzyme catalytic activities for targeted synergistic therapy of GBM. This nanozyme demonstrated dual responsiveness to alternating magnetic fields (AMF) and static magnetic fields, synergized with folic acid (FA)–mediated molecular targeting to enhance BBB penetration and achieve high-precision GBM localization. Upon simultaneous exposure to AMF and near-infrared (NIR) laser irradiation, MFCF amplified reactive oxygen species (ROS) generation, depleted glutathione, and alleviated hypoxia through synergistic magnetothermal effects, type-II photodynamic therapy, and its intrinsic multienzyme catalytic activities, ultimately inducing both ferroptosis and apoptosis. Notably, this hybrid cell-death pathway triggered immunogenic cell death, promoting the proliferation and differentiation of T cells and thereby achieving systemic immune activation. Concurrently, it reprogrammed M2-polarized macrophages into pro-inflammatory M1 phenotypes, remodeling the immunosuppressive TME and enhancing antitumor immunotherapy. Furthermore, the excellent superparamagnetism of MFCF enabled T₂-weighted magnetic resonance imaging (MRI)-guided treatment monitoring. Overall, this work presents a multifunctional nanoplatform that overcomes BBB and TME barriers to enable precise, immunomodulatory therapy for GBM.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102363"},"PeriodicalIF":10.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering micelles with hydrophilic-lipophilic balance to overcome intestinal barrier for oral therapeutic application","authors":"Kedong Liu ,&nbsp;Pi Zhao ,&nbsp;Yun Chen ,&nbsp;Yu Zhang ,&nbsp;Jian Jin ,&nbsp;Tao Wan","doi":"10.1016/j.mtbio.2025.102369","DOIUrl":"10.1016/j.mtbio.2025.102369","url":null,"abstract":"<div><div>The primary challenge in developing oral nanocarriers lies in achieving a balance between mucus penetration and cellular endocytosis. Overcoming this dilemma tends to require multiple surface properties on design of nanocarriers, but it is not favorable to clinical translation due to the complex preparation procedure and availability of commercial material. Herein, we innovatively constructed a hydrophilic-lipophilic balanced micelles only composed of poly (lactic acid)-b-poly (ethylene glycol) (PLA-PEG) or poly (lactic acid)-b-poly (carboxybetaine) (PLA-PCB) for oral delivery. The hydrophobic core of micelles was reasonably exposed by adjusting the size and the molar mass ratio of hydrophilic to hydrophobic segment of polymer, and significantly enhanced cellular internalization were observed in both micelles. In addition, the hydrophobic force driven by the core of micelles was multiply confirmed as the primary factor in enhancing cellular uptake, while time-dependent endocytosis of micelles was also verified. Although the hydrophilic segment of micelles exhibited limited functionality during the adsorption-endocytosis process of micelles, their construction could significantly mediate the intracellular trafficking process. Both <em>in vivo</em> and <em>ex vivo</em> imaging suggest that micelles exhibited good retention abilities in small intestine as well as colon after gavage administration. Remarkably, the oral bioavailability of paclitaxel (PTX) in both PTX-loaded micelles exceeded 29 % and exhibited significant oral antitumor efficacy, indicating excellent potential for oral delivery via micelles. Furthermore, poly (butyric ester)-based micelles were much capable of relieving symptoms in colitis mice induced with dextran sulfate sodium salt (DSS). These results reveal that the micelles with hydrophilic-lipophilic balance possess a broad-spectrum oral therapeutic potential and are available in potential clinical practice.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102369"},"PeriodicalIF":10.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}