Junlin Lv , Meng Li , Xiaomin Wang , Liang Zhang , Dan Han , Xiaodan Hao , Xiao Xu , Yiwei Xu , Yan Tang , Zhen Shang , Nailong Pan , Xiaoying Kong , Wenhua Xu
{"title":"4D-printed hydrogel with precise regulation of viability and environment of stem cells for diabetic skin wound healing","authors":"Junlin Lv , Meng Li , Xiaomin Wang , Liang Zhang , Dan Han , Xiaodan Hao , Xiao Xu , Yiwei Xu , Yan Tang , Zhen Shang , Nailong Pan , Xiaoying Kong , Wenhua Xu","doi":"10.1016/j.mtbio.2025.102366","DOIUrl":"10.1016/j.mtbio.2025.102366","url":null,"abstract":"<div><div>Diabetic wounds not only suffer from vascular and nerve damage, but also face the severe challenge of impaired stem cell activity. In recent years, although traditional tissue engineering strategies provide exogenous stem cells for the healing of diabetic wounds, they have not reversed the dilemma of stem cell proliferation and differentiation in a high-glucose environment. In this work, piRNA-hsa-32182 was first demonstrated to be highly expressed in diabetic wounds and significantly inhibit the differentiation and migration of adipose-derived mesenchymal stem cells (ADMSCs). Accordingly, a 4D-printed tissue engineering hydrogel and piRNA-hsa-32182 antagomir were prepared to precisely modulate the survival microenvironment of ADMSCs and accelerate diabetic wound healing. 4D printed tissue engineering hydrogels provided a highly ordered microenvironment for ADMSCs through internal space homogenization, thereby effectively improving the loading rate and survival rate of stem cells. In addition, piRNA-hsa-32182 antagomir effectively enhanced the migration of ADMSCs, thereby increasing the deposition and maturation of collagen on the wound and promoting angiogenesis. In summary, this study significantly improved the microenvironment of wounds through the synergy of bio-intelligent printing technology and gene expression regulation, providing a new clinical paradigm for the treatment of diabetic wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102366"},"PeriodicalIF":10.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221344","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}
Wen Xiao , Shugang Qin , Xuehui Li , Xinyang Jin , Aiwei Zhu , Xi He , Xing Duan , Yuting Chen , Yupei Zhang , Na Fan , Qian Zheng , Guohong Li , Zhongshan He , Kepan Chen , Hai Huang , Xiawei Wei , Christiane Moog , Bin Su , Xiangrong Song
{"title":"Tomatine as a versatile adjuvant boosts mRNA vaccine responses","authors":"Wen Xiao , Shugang Qin , Xuehui Li , Xinyang Jin , Aiwei Zhu , Xi He , Xing Duan , Yuting Chen , Yupei Zhang , Na Fan , Qian Zheng , Guohong Li , Zhongshan He , Kepan Chen , Hai Huang , Xiawei Wei , Christiane Moog , Bin Su , Xiangrong Song","doi":"10.1016/j.mtbio.2025.102360","DOIUrl":"10.1016/j.mtbio.2025.102360","url":null,"abstract":"<div><div>The potent adaptive immune response of mRNA vaccines requires that sufficient antigens translated from mRNA cargos and highly efficient activation of innate immunity. However, it remains unclear if simple introduction of an adjuvant can help mRNA vaccines achieve these functions. In this study, a nature product, tomatine, was experimentally incorporated into the widely used nanocarriers, serving a multi-functional adjuvant to improve mRNA expression efficiency and activate innate immunity. Tomatine based liposome (T-LPX) exhibited elevated uptake in dendritic cells (DCs) via caveolin-mediated endocytosis and improved mRNA translation via the increased expression of DExH-box helicase 29 mediated by tomatine, leading to a marked increase in mRNA expression efficiency and ensuring highly efficient antigen presentation. Additionally, tomatine was shown to activate nucleotide-binding oligomerization domain (NOD)-like receptor pathway, thereby promoting the secretion of IFN-<em>γ</em> and upregulating the co-stimulatory molecules (CD80 and CD86) in DCs. Finally, T-LPX loaded with a tumor antigen-encoding mRNA was investigated and found to elicit potent immune responses against the E.G7-OVA murine tumor. Furthermore, such versatile adjuvant effect of tomatine was also demonstrated to equally apply to the other nanocarrier (lipid nanoparticle) and antigen. The tomatine-based LNP-mRNA vaccine against SARS-CoV-2 presented enduring humoral and cellular immune responses. These findings underscore tomatine’s potential as a versatile adjuvant for mRNA nano-vaccines, with promising applications in both cancer therapy and infectious disease prevention.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102360"},"PeriodicalIF":10.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221348","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}
Bowen Dai , Haoyu Yu , Tao Zhang , Kun Wang , Wei Xiong , Zhaojian Gong , Tianhan Kai
{"title":"Electro-activated nanozyme for in situ tumor vaccination: Synergistic multi-enzyme catalysis and electrodynamic therapy","authors":"Bowen Dai , Haoyu Yu , Tao Zhang , Kun Wang , Wei Xiong , Zhaojian Gong , Tianhan Kai","doi":"10.1016/j.mtbio.2025.102344","DOIUrl":"10.1016/j.mtbio.2025.102344","url":null,"abstract":"<div><div>Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis and limited treatment options. To address the challenges of conventional therapy resistance, antioxidant defence, and immune evasion, we developed a multifunctional nanozyme platform, MIL-100(Fe)@Pt@R837@HA (HMPR), that integrates electrodynamic therapy (EDT), chemodynamic therapy, and immunotherapy. The multi-enzyme activities of HMPR allow for the oxygen generation, hydroxyl radicals production, and glutathione depletion, thereby alleviating hypoxia and triggering both apoptosis and ferroptosis. Under electrical stimulation, HMPR promotes significant production of reactive oxygen species via Pt-mediated EDT to amplify ferroptosis and immunogenic cell death (ICD). In addition, the tumor-specific GSH level triggers the release of the immune adjuvant R837. The potent ICD effect, combined with the sustained release of the adjuvant R837, endows the nanozyme HMPR with the characteristics of an in situ “tumor vaccine”, continuously promoting dendritic cell maturation, activating T cell-mediated immunity, and establishing long-term immunological memory to prevent tumor recurrence and inhibition of distant tumor growth. This cascade effect reprograms the immunosuppressive tumor microenvironment into an immunostimulatory one, significantly enhancing the efficacy of PD-1 blockade. Our study provides a powerful electro-enhanced nanozyme-immune synergistic strategy for OSCC and offers a flexible platform adaptable to other solid tumors.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102344"},"PeriodicalIF":10.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221355","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}
Michelle A. Trempel , Yimei Du , Louis P. Widom , Emily E. Reitz , Alexis M. Feidler , Pelin Kasap , Britta Engelhardt , Thomas R. Gaborski , Harris A. Gelbard , Niccolo Terrando , James L. McGrath
{"title":"Pericytes repair engineered defects in the basement membrane to restore barrier integrity in an in vitro model of the blood-brain barrier","authors":"Michelle A. Trempel , Yimei Du , Louis P. Widom , Emily E. Reitz , Alexis M. Feidler , Pelin Kasap , Britta Engelhardt , Thomas R. Gaborski , Harris A. Gelbard , Niccolo Terrando , James L. McGrath","doi":"10.1016/j.mtbio.2025.102361","DOIUrl":"10.1016/j.mtbio.2025.102361","url":null,"abstract":"<div><div>Pericytes play a key role in the brain where they support brain microvascular endothelial cells (BMECs) in forming the tightly regulated blood-brain barrier (BBB). The loss of pericytes, and corresponding weakening of the BBB, has been reported in response to episodes of systemic inflammation and in neurodegenerative disease. We recently demonstrated that iPSC-derived pericyte-like and BMEC-like cells form a nascent, 3D basement membrane when cultured across an ultrathin (100 nm thick) and highly nanoporous membrane (McCloskey, Ahmed et al., AHCM 2024). We also concluded that the pericyte-like cells did not contribute soluble factors to enhance permeability. Given the structural role of pericytes <em>in vivo</em>, here we sought to engineer defects in the basement membrane to see if pericytes could repair them. In BMEC-like monocultures, we found that micropore (3 μm and 5 μm) patterns in nanomembranes appeared as corresponding discontinuities in basement membrane laminin and destabilized barrier function. Both the laminin defects and the baseline barrier function were restored with the addition of pericytes on the basal side of the membrane. We further found that: 1) BMECs transmigrate through large micropores in monocultures but not in co-culture with pericytes, and 2) pericytes stabilized barrier function. Our results align with the role of pericytes as structural support cells for the microvasculature and encourage the use of our tissue barrier platform (the μSiM) to model acute and chronic neurological disorders involving pericyte dysfunction and/or disruption of basement membrane integrity.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102361"},"PeriodicalIF":10.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221451","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}
Linxue Zhang , Xing He , Hongyu Zhu , Qi Sun , Yu Liu , Lin Huang , Tianlong Wen , Jianfu Li , Zhongwen Lan , Zhong Yu , Zhenglin Yang , Kun Jia , Ke Sun , Ziyan Wang
{"title":"Injectable magnetic hydrogel induces multi-programmed cell death and deep tumor regression in magnetic hyperthermia therapy in hepatocellular carcinoma","authors":"Linxue Zhang , Xing He , Hongyu Zhu , Qi Sun , Yu Liu , Lin Huang , Tianlong Wen , Jianfu Li , Zhongwen Lan , Zhong Yu , Zhenglin Yang , Kun Jia , Ke Sun , Ziyan Wang","doi":"10.1016/j.mtbio.2025.102341","DOIUrl":"10.1016/j.mtbio.2025.102341","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains global health concern due to complex pathogenic mechanism and lack of effective therapeutic drugs. The magnetic hyperthermia therapy (MHT) appears as the promising and safe strategy during the recent exploration of new technology for cancer treatment. Herein, we reported an injectable and magnetic-hydrogel-construct-based thermal regression agent mPEG-<em>b</em>-PLV-Fe<sub>3</sub>O<sub>4</sub> Hybrids in MHT for the first time. Percutaneous thermotherapy was employed as a minimally invasive strategy for treating hepatic tumors in a rabbit model. Based on the evidence in vitro and in vivo studies, we demonstrated that mPEG-<em>b</em>-PLV-Fe<sub>3</sub>O<sub>4</sub> Hybrids under magnetic field, exhibited powerful antitumor effect by inducing massive ROS accumulation, severe lipid peroxidation and damaged mitochondria, which together triggered triple forms of cell death: ferroptosis, autophagy and apoptosis. Furthermore, we revealed that mPEG-<em>b</em>-PLV-Fe<sub>3</sub>O<sub>4</sub> Hybrids under magnetic field reprogramed the cysteine-glutathione metabolism by suppressing SLC7A11 expression, which aggravated redox imbalance and suppresses cell survival. The hybrids achieve outstanding therapeutic results in mouse and rabbit models. Our findings underscore that mPEG-<em>b</em>-PLV-Fe<sub>3</sub>O<sub>4</sub> Hybrids under magnetic field is a promising strategy for cancer therapy by targeting the SLC7A11-cysteine-glutathione axis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102341"},"PeriodicalIF":10.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221350","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}
Zhirong Liu , Xiaobin Ren , Bai Sun , Guangdong Zhou , Hui Gao , Jiejing Bi , Zelin Cao , Kaikai Gao , Hui Ma , Lu Ye
{"title":"An innovative diagnostic method for myopia using blood-based biomemristor","authors":"Zhirong Liu , Xiaobin Ren , Bai Sun , Guangdong Zhou , Hui Gao , Jiejing Bi , Zelin Cao , Kaikai Gao , Hui Ma , Lu Ye","doi":"10.1016/j.mtbio.2025.102350","DOIUrl":"10.1016/j.mtbio.2025.102350","url":null,"abstract":"<div><div>Myopia has become one of the main factors affecting the healthy growth of adolescents. However, the current methods for diagnosing myopia based on physiological indicators are still blank. In this work, a memristive device with Ag/ZIF-8:PVP/FTO structure was developed using ZIF-8 as the main functional material for detecting and distinguishing physiological states associated with high myopia. We observe the as-prepared memristor exhibits a significant <em>I-V</em> curve with memristive characteristics, as well as stable bipolar resistance switching and voltage dependent multi mechanism conduction behavior. Furthermore, after optimizing the system parameters, a robust multi-level switching response was achieved, in which the biomemristor manufactured from blood samples of highly myopic patients showed atypical memory blockade, indicating an interruption in ions migration and trap state dynamics. In particular, the experiment using a monozygotic twin family model has shown that altered memristive behavior is closely related to phenotypic differences rather than genetic identity, highlighting the sensitivity of the device to subtle physiological changes. Therefore, this work has achieved for the first time the application of the memristor based on ZIF-8 in myopia detection, which brings great hope for early screening, phenotype stratification, and minimally invasive monitoring of pediatric and high-risk populations.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102350"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155487","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}
Yuxi Bai , Nannan Wu , Xinyu Li , Zhiwei Liu , Kun Li , Tifeng Jiao , Fei Liu
{"title":"Recent progress of 3D printed responsive scaffolds for bone repair: A review","authors":"Yuxi Bai , Nannan Wu , Xinyu Li , Zhiwei Liu , Kun Li , Tifeng Jiao , Fei Liu","doi":"10.1016/j.mtbio.2025.102351","DOIUrl":"10.1016/j.mtbio.2025.102351","url":null,"abstract":"<div><div>Bone defects are complex in etiology, extensive in scope, and associated with local microenvironmental disruption, leading to issues such as donor site complications, poor biocompatibility, and inadequate functional recovery with traditional treatment methods (e.g., autologous bone transplantation, metal implants). Bone repair scaffolds have garnered widespread attention due to their excellent biomimetic properties and high repair efficiency. With the advantages of personalization, high-precision manufacturing and complex structure forming, 3D printing technology has shown great potential for application in the field of bone restoration. In contrast to conventional bone scaffolds, responsive scaffolds emulate the dynamic environment of the natural extracellular matrix, which can produce controlled effects in responding to stimuli, hence promoting cell multiplication and differentiation and bone regeneration. This review introduces the study of human bone structure and defects, summarizes the 3D printing technologies of preparing bone scaffolds, concludes the characteristics and applicability of different 3D printing technologies, then the applications of light, piezoelectric, temperature, immune, magnetic, and enzyme-responsive scaffolds in the field of bone repair are summarized according to the types of responses of bone scaffolds to various types of stimuli in the human body, and finally the problems faced by responsive scaffolds in the process of clinical translation are pointed out.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102351"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155467","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}
Xiaoxiao Li , Xiangwei Li , Dandan Zhou , Yanqin Xu , Biemin Sun , Yanzhu Hu , Yibo Zhu , Junxian Hu , Zeyu Pang , Chen Zhao , Yongjian Gao , You Long , Pei Li , Qiang Zhou , Yiyang Wang
{"title":"Bottom-up engineering of the nucleus pulposus using a photocrosslinkable decellularized matrix hydrogel attenuates inflammaging and enhances microtissue-mediated regeneration","authors":"Xiaoxiao Li , Xiangwei Li , Dandan Zhou , Yanqin Xu , Biemin Sun , Yanzhu Hu , Yibo Zhu , Junxian Hu , Zeyu Pang , Chen Zhao , Yongjian Gao , You Long , Pei Li , Qiang Zhou , Yiyang Wang","doi":"10.1016/j.mtbio.2025.102347","DOIUrl":"10.1016/j.mtbio.2025.102347","url":null,"abstract":"<div><div>Degenerative disc disease (DDD), characterized by the pathological deterioration of nucleus pulposus (NP) tissue, affects millions globally. Tissue engineering strategies offer potential to create tissue-engineered NP (TE-NP) analogs to address DDD. However, traditional \"top-down' approaches face challenges in achieving uniform cell distribution and replicating the intradiscal extracellular matrix (ECM) environment. In contrast, a \"bottom-up' strategy utilizing microscale seed units represents a promising alternative. This study introduces an innovative \"bottom-up' approach for constructing TE-NP, leveraging bioreactor-cultivated NP microtissues (NP-MTs) as seed units and a novel methacrylate-modified decellularized nucleus pulposus matrix (DNPM-MA) hydrogel as a supporting biomaterial. NP-MTs cultivated under low-magnitude hydrostatic pressure exhibit nascent ECM surroundings adapting well to the intradiscal microenvironment. The DNPM-MA hydrogel, with its compositional and mechanical attributes, supports the growth, migration, proliferation, and ECM synthesis of NP-MTs, making it an ideal biomaterial for long-term cultivation. The combination of NP-MTs and the DNPM-MA hydrogel yielded superior tissue regeneration outcomes both in vitro and in vivo. Transcriptome and molecular assessments revealed a correlation between the biological properties of the DNPM-MA hydrogel and the attenuation of inflammaging within encapsulated NP-MTs. Overall, this innovative \"bottom-up' constructed TE-NP exhibits superior regenerative potential and is a promising tissue engineering strategy for treating DDD.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102347"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221352","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}
Zheng-Hong Chen , Ye-Rong Hu , Xing-Bo Yue , Kun Zhao , Huan Yang , Zhi-Gang Liu , Rui Xu , Wei-Dong Lü
{"title":"Matrix-bound nanovesicles isolated from decellularized tumors as platforms for targeting parent tumor cells and tumor-associated stromal cells","authors":"Zheng-Hong Chen , Ye-Rong Hu , Xing-Bo Yue , Kun Zhao , Huan Yang , Zhi-Gang Liu , Rui Xu , Wei-Dong Lü","doi":"10.1016/j.mtbio.2025.102355","DOIUrl":"10.1016/j.mtbio.2025.102355","url":null,"abstract":"<div><div>Matrix-bound nanovesicles (MBVs) are an emerging class of extracellular vesicles (EVs) that are integrated into the extracellular matrix (ECM). Tumor ECM-derived MBVs hold promise as platforms for targeted delivery of therapeutic agents to both parental tumor cells and surrounding stromal cells. In this study, a subcutaneous tumor model was established by implanting A549 human lung adenocarcinoma cells into immunodeficient mice. The mixed method was used to decellularize the tumor tissue, producing an ECM scaffold free of cellular components. Subsequently, MBVs were successfully isolated from the ECM of the decellularized tumors. Compared with tumor cell-derived liquid-phase EVs, acellular tumor MBVs were smaller in size and were demonstrated to transport proteins related to focal adhesion and protein binding. The in vitro binding affinity assays and cell culture experiments involving acellular tumor MBVs showed specific targeting affinity for ECM components, tumor cells, and tumor-associated stromal cells, including cancer-associated fibroblasts and tumor-associated macrophages. After loading of the drug doxorubicin, this platform selectively inhibited tumor cells and tumor-associated stromal cells both in vitro and in vivo. These results provide important insights for future research on the potential role of tumor ECM-derived MBVs in targeted cancer therapy and the modulation of premetastatic niches.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102355"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221359","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}
Yihan Wu , Chenglin He , Yu Huang , Zhen Liu , Ying Zhu , Manyin Zhang , Jingjing Li , Yu You , Yitao Wang , Tao Chen , Jinming Zhang
{"title":"Glycyrrhizic acid-based nanotheranostic system to enhance photothermal immunotherapy by suppressing HSP90 and remodeling tumor microenvironment","authors":"Yihan Wu , Chenglin He , Yu Huang , Zhen Liu , Ying Zhu , Manyin Zhang , Jingjing Li , Yu You , Yitao Wang , Tao Chen , Jinming Zhang","doi":"10.1016/j.mtbio.2025.102353","DOIUrl":"10.1016/j.mtbio.2025.102353","url":null,"abstract":"<div><div>Anticancer photothermal therapy efficacy is currently restricted by heat shock protein (HSP90)-mediated thermoresistance, immunosuppressive microenvironment, and poor delivery efficiency of photosensitizers. At present, the “all-in-one” therapeutic system that can simultaneously achieve tumor-targeted delivery, efficient photothermal therapy, and tumor immune enhancement effects is desperately needed. We previously fabricated Glycyrrhizic acid (GL)-based lipid nanoparticles (GLPs) that possess hepatocellular carcinoma (HCC) targeting and improved membrane stability. Interestingly, GL exhibits the potential to inhibit the up-regulated HSP90 and regulate the immunosuppressive tumor microenvironment. Herein, the near-infrared photosensitizer IR780 was efficiently encapsulated into GLPs to promote photothermal enhancement and synergistic immunosuppressive anti-tumor effects. Under the irradiation of NIR light, the IR780 GLPs effectively enhance the PTT efficacy on the HCC-bearing mice model via suppressing HSP90 expression with the combination of GL. Furthermore, IR780 GLPs exhibited strong HCC targeting ability, effectively downregulating the expression of immunosuppressive Treg cells, promoting the repolarization of M2 macrophages to M1 macrophages, increasing the infiltration of cytotoxic CD8<sup>+</sup>T cells and downregulating the expression of TGF-β and IL-10, upregulating IL-12, TNF-α, and IFN-γ, reshaping the tumor immunosuppressive microenvironment. Overall, we developed a novel GL-based lipid nanoparticle system encapsulating IR780 to amplify the synergistic effects of chemo-PTT for HCC treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102353"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155490","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}