Journal of Nanobiotechnology最新文献

{"title":"miRNA let-7f-5p-encapsulated labial gland MSC-derived EVs ameliorate experimental Sjögren's syndrome by suppressing Th17 cells via targeting RORC/IL-17A signaling axis.","authors":"Yufei Xie, Maosheng Chai, Yixiao Xing, Peiru Zhou, Pan Wei, Hong Hua","doi":"10.1186/s12951-025-03308-y","DOIUrl":"10.1186/s12951-025-03308-y","url":null,"abstract":"<p><p>Sjögren's syndrome (SS) is an autoimmune disease primarily affecting salivary glands, with xerostomia as a distinct clinical manifestation. This disease also poses a significantly increased risk of lymphoma, severely impacting patients' quality of life. The imbalance between Th17 and Treg cells plays a critical role in SS progression, driving severe immune dysregulation, chronic inflammation, and escalating tissue dysfunction. However, current clinical treatments for SS still remain limited, and it continues to be recognized as a refractory disease. Therefore, the development of novel and effective therapeutic strategies is a pressing demand in clinical research. In recent years, extracellular vesicle (EV) therapy has emerged as a promising approach for autoimmune disease treatment, showing encouraging outcomes in modulating immune balance and alleviating symptoms. EVs carry diverse cargo, among which microRNAs (miRNAs) are highly abundant and play critical roles. These small RNAs are essential for EV-mediated functions, particularly in regulating gene expression and modulating the immune microenvironment. Our research team first isolated labial gland mesenchymal stem cells (LGMSCs) and their derived EVs (LGMSC-EVs), which offer potential therapeutic advantages in SS due to their salivary gland origin. Then we screened and identified the highly enriched miRNA let-7f-5p as a key regulator through miRNA profiling analysis. To achieve better therapeutic outcomes, we transfected exogenous miRNA let-7f-5p into LGMSC-EVs to upregulate its expression, thereby constructing let-7f-5p-encapsulated LGMSC-EVs. These modified EVs were subsequently tested in an experimental SS mouse model to evaluate their therapeutic potential. The upregulation of miRNA let-7f-5p in LGMSC-EVs significantly enhanced their therapeutic effects, resulting in clinical improvements such as increased salivary flow and reduced lymphocytic infiltration. Mechanistically, let-7f-5p-encapsulated LGMSC-EVs suppressed Th17 cells by directly targeting the 3'-untranslated region (3'UTR) of RORC, inhibiting the RORC/IL-17A signaling axis, and reducing IL-17A production, thereby restoring Th17/Treg balance and promoting an anti-inflammatory profile. Collectively, this let-7f-5p-encapsulated LGMSC-EV therapy offers a promising target-driven approach for the treatment of SS, achieving improved clinical outcomes and immune rebalance after modification with miRNA let-7f-5p, which presents new potential for the clinical treatment of SS.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"228"},"PeriodicalIF":10.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZnO-Cu/Mn nanozyme for rescuing the intestinal homeostasis in Salmonella-induced colitis.","authors":"Aimin Wu, Chen Liang, WenShuang Chen, ChangFang Lu, JunZhou Chen, Bing Wu, Daiwen Chen, Li He, Xianxiang Wang","doi":"10.1186/s12951-025-03283-4","DOIUrl":"10.1186/s12951-025-03283-4","url":null,"abstract":"<p><p>Salmonella is one of the most common foodborne pathogens, which can cause severe enteritis and intestinal microbiota imbalance. However, there are limited strategies currently available for preventing or treating Salmonella-induced colitis. Herein, we developed the Cu/Mn-co-doped ZnO tandem nanozyme (ZnO-CM) with pH-responsive multienzyme-mimicking activities via doping engineering for the treatment of Salmonella-induced colitis. Benefiting from the co-doping of Cu and Mn, ZnO-CM nanospheres exhibit remarkable peroxidase-like activity in acidic condition and superoxide dismutase- and catalase-like activities in neutral environment. Animal experiments show that ZnO-CM can efficiently inhibit bacterial growth, alleviate inflammation, and restore the intestinal barrier, resulting in good antibacterial and anti-inflammatory effects on Salmonella-induced colitis. Mechanistically, ZnO-CM functions through inhibiting the continuous accumulation of ROS, increasing the levels of tight junction proteins occludin and claudin-1, and decreasing the expression of pro-inflammatory cytokines IL-1β and IL-6 in intestine. This work not only presents an effective paradigm for Salmonella-induced colitis therapy, but also provides new sights into the prevention and treatment of other bacterial enteritis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"225"},"PeriodicalIF":10.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium nanoparticles activate selenoproteins to mitigate septic lung injury through miR-20b-mediated RORγt/STAT3/Th17 axis inhibition and enhanced mitochondrial transfer in BMSCs.","authors":"Wan-Jie Gu, Feng-Zhi Zhao, Wei Huang, Ming-Gao Zhu, Hai-Yan Huang, Hai-Yan Yin, Tianfeng Chen","doi":"10.1186/s12951-025-03312-2","DOIUrl":"10.1186/s12951-025-03312-2","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with complex inflammatory pathogenesis. While bone marrow mesenchymal stem cells (BMSCs) demonstrate therapeutic potential through anti-inflammatory and cytoprotective effects, their age-related functional decline limits clinical utility. This study developed chitosan-functionalized selenium nanoparticles (SeNPs@CS, 100 nm) to rejuvenate BMSCs through miR-20b-mediated selenoprotein biosynthesis. Mechanistic investigations revealed that SeNPs@CS-treated BMSCs exhibited enhanced mitochondrial transfer capacity, delivering functional mitochondria to damaged alveolar epithelial cells (AECII) for cellular repair. Concurrently, miR-20b upregulation suppressed the RORγt/STAT3/Th17 axis, reducing pro-inflammatory Th17 cell differentiation in CD4⁺ T lymphocytes. The dual-target mechanism integrates immunomodulation via Th17 pathway inhibition with mitochondrial rejuvenation therapy, representing a paradigm-shifting approach for ALI management. These engineered BMSCs mitigated inflammatory markers in murine models, demonstrating superior efficacy to conventional BMSC therapies. Our findings establish SeNPs@CS-modified BMSCs as a novel therapeutic platform combining nanotechnology-enhanced stem cell engineering with precision immunometabolic regulation, providing new avenues for the treatment of sepsis-induced ALI.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"226"},"PeriodicalIF":10.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing severity of inflammatory bowel disease through colonization of Lactiplantibacillus plantarum and its extracellular vesicles release.","authors":"Yuanyuan Wu, Xinyue Huang, Qianbei Li, Chaoqun Yang, Xixin Huang, Hualongyue Du, Bo Situ, Lei Zheng, Zihao Ou","doi":"10.1186/s12951-025-03280-7","DOIUrl":"10.1186/s12951-025-03280-7","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is characterized by compromised intestinal barrier function and a lack of effective treatments. Probiotics have shown promise in managing IBD due to their ability to modulate the gut microbiota, enhance intestinal barrier function, and exert anti-inflammatory effects. However, the specific mechanisms through which probiotics exert these therapeutic effects in IBD treatment remain poorly understood. Our research revealed a significant reduction of Lactiplantibacillus plantarum (L. plantarum) in the gut microbiota of IBD patients. L. plantarum is a well-known probiotic strain in the list of edible probiotics, recognized for its beneficial effects on gut health, including its ability to strengthen the intestinal barrier and reduce inflammation. We demonstrated that supplementation with L. plantarum could alleviate IBD symptoms in mice, primarily by inhibiting apoptosis in intestinal epithelial cells through L. plantarum's bacterial extracellular vesicles (L. plant-EVs). This protective effect is dependent on the efficient uptake of L. plant-EVs by intestinal cells. Intriguingly, watermelon enhances L. plantarum colonization and L. plant-EVs release, further promoting intestinal barrier repair. Our findings contribute to the understanding of L. plant-EVs in the probiotic-based therapeutic approach for IBD, as they are promising candidates for nanoparticle-based therapeutic methods that are enhanced by natural diets such as watermelon. This study thereby offers a potential breakthrough in the management and treatment of IBD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"227"},"PeriodicalIF":10.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of salt solution on the physicochemical properties and in vitro/ in vivo expression of mRNA/LNP.","authors":"Siyuan Tang, Lei Huang, Jiahao Ge, Jie Li, Mingxia Qiu, Yiqing Zhang, Mei Long, Gang Wu, Rui Zhang, Xueyun Ma, Qiang Xia, Ping Wan, Taihua Yang","doi":"10.1186/s12951-025-03318-w","DOIUrl":"10.1186/s12951-025-03318-w","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) have revolutionized nucleic acid delivery, enabling significant advances in mRNA-based therapeutics. While extensive research has focused on lipid composition, the impact of preparation solutions on LNP performance remains underexplored. This study systematically investigated the effects of pH, salt type, and concentration across key preparation solutions-mRNA aqueous, dilution, exchange, and storage solutions-on the physicochemical properties, stability, and expression efficiency of SM102-based mRNA/LNPs. Findings revealed that the pH of the mRNA aqueous solution was critical, with a pH of 4 optimizing encapsulation efficiency (EE) and cellular expression. The exchange solution's pH significantly influenced biodistribution, particularly liver-specific expression following intravenous and intramuscular administration. Sucrose was identified as essential for freeze-thaw stability, with a 300 mM concentration minimizing aggregation and mRNA leakage. Furthermore, preparation solutions were shown to influence the structural integrity of LNPs, impacting their in vivo and in vitro performance. These insights highlight the importance of preparation conditions in optimizing LNP formulations for clinical applications, offering a foundation for enhanced therapeutic design and delivery.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"223"},"PeriodicalIF":10.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional glycyrrhizic acid-loaded nanoplatform combining ferroptosis induction and HMGB1 blockade for enhanced tumor immunotherapy.","authors":"Xuan Sha, Chuanbing Wang, Yang Liu, Nan Zhong, Yishi Lu, Qi Zhang, Shangyu Lu, Doudou He, Yingying Jin, Yuxia Tang, Shouju Wang","doi":"10.1186/s12951-025-03307-z","DOIUrl":"10.1186/s12951-025-03307-z","url":null,"abstract":"<p><p>Inducing ferroptotic cell death has been recognized as a promising approach in cancer therapy. However, ferroptosis can provoke tumor infiltration by myeloid-derived suppressor cells (MDSCs) through HMGB1 secretion, causing a tumor suppressive immune response. On the other hand, ferroptosis also occurs the immune cells due to its non-selective properties, which can compromise anti-tumor immunity. To address these challenges, a two-pronged approach is proposed, encompassing selectively triggered ferroptosis in tumor cells and HMGB1 blockade, aimed at eliciting systemic anti-tumor immunity and alleviating immunosuppression. Herein, GSH-specific driven nanoplatform is composed of uniform FeOOH nanospindles coated with tetrasulfide bond-bridged mesoporous organosilica (DMOS) shell, and loaded with the HMGB1 inhibitor, glycyrrhizic acid (GA). This nanoplatform is endowed with high glutathione (GSH) depletion efficiency and exhibits highly efficient Fe²⁺ and ROS generation capacity, which promotes the accumulation of LPO and subsequently induces ferroptosis. Concurrently, the inhibition of HMGB1 release counteracts the immunosuppressive effects within the tumor microenvironment. This innovative nanoplatform effectively suppresses the growth of 4T1 tumors and notably enhancing the therapeutic outcomes of immune checkpoint blockade across experimental data. The collective findings indicate its potential as a reliable therapeutic strategy for boosting ferroptosis-mediated tumor immunity with favorable safety profiles.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"224"},"PeriodicalIF":10.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-499a-5p from human umbilical cord mesenchymal stem cells attenuates liver fibrosis via targeting ETS1/GPX4-mediated ferroptosis in hepatic stellate cells.","authors":"Zheng Wang, Mengqin Yuan, Lichao Yao, Zhiyu Xiong, Kai Dai, Pingji Liu, Ping Chen, Muhua Sun, Kan Shu, Yuchen Xia, Yingan Jiang","doi":"10.1186/s12951-025-03291-4","DOIUrl":"10.1186/s12951-025-03291-4","url":null,"abstract":"<p><p>Liver fibrosis is a leading cause of liver-related mortality worldwide, yet effective therapies remain limited. Mesenchymal stem cells (MSCs) have recently shown promise in treating liver fibrosis due to their anti-inflammatory and anti-fibrotic properties. However, the precise molecular mechanisms by which MSCs exert their effects remain unclear. In this study, we explored how human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) contribute to treating liver fibrosis, and revealed a crucial role of ferroptosis in modulating hepatic stellate cells (HSCs) activity. We found that MSCs primarily promote ferroptosis in HSCs in an exosome-dependent manner. Specifically, MSC-derived exosomes (MSC-Exos) deliver miR-499a-5p, which interacts with the transcription factor ETS1, leading to the suppression of GPX4, a key regulator of ferroptosis, thereby reducing the fibrogenic activity of HSCs. Overexpression of ETS1 in HSCs counteracted miR-499a-5p-induced ferroptosis, underscoring the pathway's potential as a target for therapeutic intervention. Furthermore, molecular docking simulations further identified optimal ETS1-GPX4 binding sites. This research uncovers a novel mechanism by which MSCs may treat liver fibrosis, providing insights that could guide the development of more effective therapies for this widespread condition.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"222"},"PeriodicalIF":10.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunogenic potential of an optimized mRNA lipid nanoparticle formulation carrying sequences from virus and protozoan antigens.","authors":"Renata S Fernandes, Gabriela de Assis Burle-Caldas, Sarah Aparecida Rodrigues Sergio, Ana Flávia Bráz, Nathália Pereira da Silva Leite, Milton Pereira, Juliana de Oliveira Silva, Natália Satchiko Hojo-Souza, Bianca de Oliveira, Ana Paula S Moura Fernandes, Flávio Guimarães da Fonseca, Ricardo Tostes Gazzinelli, Diego Dos Santos Ferreira, Santuza M Ribeiro Teixeira","doi":"10.1186/s12951-025-03201-8","DOIUrl":"10.1186/s12951-025-03201-8","url":null,"abstract":"<p><strong>Background: </strong>Lipid nanoparticles (LNP) are a safe and effective messenger RNA (mRNA) delivery system for vaccine applications, as shown by the COVID-19 mRNA vaccines. One of the main challenges faced during the development of these vaccines is the production of new and versatile LNP formulations capable of efficient encapsulation and delivery to cells in vivo. This study aimed to develop a new mRNA vaccine formulation that could potentially be used against existing diseases as well as those caused by pathogens that emerge every year.</p><p><strong>Results: </strong>Using firefly luciferase (Luc) as a reporter mRNA, we evaluated the physical-chemical properties, stability, and biodistribution of an LNP-mRNA formulation produced using a novel lipid composition and a microfluidic organic-aqueous precipitation method. Using mRNAs encoding a dengue virus or a Leishmania infantum antigen, we evaluated the immunogenicity of LNP-mRNA formulations and compared them with the immunization with the corresponding recombinant protein or plasmid-encoded antigens. For all tested LNP-mRNAs, mRNA encapsulation efficiency was higher than 85%, their diameter was around 100 nm, and their polydispersity index was less than 0.3. Following an intramuscular injection of 10 µg of the LNP-Luc formulation in mice, we detected luciferase activity in the injection site, as well as in the liver and spleen, as early as 6 h post-administration. LNPs containing mRNA encoding virus and parasite antigens were highly immunogenic, as shown by levels of antigen-specific IgG antibody as well as IFN-γ production by splenocytes of immunized animals that were similar to the levels that resulted from immunization with the corresponding recombinant protein or plasmid DNA.</p><p><strong>Conclusions: </strong>Altogether, these results indicate that these novel LNP-mRNA formulations are highly immunogenic and may be used as novel vaccine candidates for different infectious diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"221"},"PeriodicalIF":10.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking copper transporter protein-dependent drug efflux with albumin-encapsulated Pt(IV) for synergistically enhanced chemo-immunotherapy.","authors":"Man Fang, Lei Cao, Zhao Zhang, Zhen Yu, Yue Shen, Jieqi Chen, Juan Chen, Yue-Qin Li, Zhaoqian Liu, Yingcai Meng, Haihua Xiao, Qiang Qu, Ji-Ye Yin, Xiang-Ping Li","doi":"10.1186/s12951-025-03310-4","DOIUrl":"10.1186/s12951-025-03310-4","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) represents the most prevalent form of lung cancer, exerting a substantial impact on global health. Cisplatin-based chemotherapy is the standard treatment for NSCLC, but resistance and severe side effects present significant clinical challenges. Recently, novel tetravalent platinum compounds have attracted significant interest. While numerous studies concentrate on their functional modifications and targeted delivery, tumor-induced platinum resistance is frequently overlooked. Previous tetravalent platinum compound demonstrated antitumor activity, yet proved ineffective against cells exhibiting resistance to cisplatin. In order to enhance the efficacy and potential applications of tetravalent platinum in NSCLC, a glutathione (GSH)-responsive albumin nanoquadrivalent platinum (HSA@Pt) have been constructed. In light of previous research into drug conjugation, this study was to develop a combined chemo-immunotherapy approach. The HSA@Pt demonstrated high efficacy and low toxicity, with targeted tumor accumulation. Furthermore, Ammonium Tetrathiomolybdate (TM) has been demonstrated to exert a synergistic inhibitory effect on ATPase Copper Transporting Beta (ATP7B) and Programmed Death Ligand 1 (PD-L1), impede platinum efflux, induce cellular stress, and activate antitumor immunity. The findings suggest HSA@Pt's potential for clinical use and a novel chemo-immunotherapy strategy for NSCLC, enhancing the utility of established drugs through synergistic sensitization.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"217"},"PeriodicalIF":10.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic gold nano-modulator for deep-tumor NIR-II photothermal immunotherapy via gaseous microenvironment remodeling strategy.","authors":"Honglin Huang, Zhengxin Xie, Ningxi Li, Li Zeng, Qianyi Zeng, Ziman Yang, Jinyang Shen, Hong Yang, Yiyao Liu, Chunhui Wu","doi":"10.1186/s12951-025-03304-2","DOIUrl":"10.1186/s12951-025-03304-2","url":null,"abstract":"<p><strong>Introduction: </strong>Effective immunotherapeutic treatment of solid tumors has been greatly challenged by the complex hostile tumor immunosuppressive microenvironment (TIME), which typically involves hypoxia and immunosuppression.</p><p><strong>Methods: </strong>Herein, a multifunctional biomimetic gold nano-modulator (denoted as GNR-SNO@MMT) was developed to realize the efficient second near-infrared (NIR-II) photothermal immunotherapy via tumor targeting and deep penetration, vascular normalization and immune reprogramming. NIR-II photothermal agent gold nanorods (GNR) were grafted with thermosensitive S-nitrosothiol (SNO) donors and camouflaged with the tumor-penetrating peptide tLyp-1-modified macrophage membrane (MM) to yield GNR-SNO@MMT.</p><p><strong>Results: </strong>The engineered membrane coating increased the capacity for tumor inflammatory tropism and deep penetration, which aided GNR-SNO@MMT in ablating tumors together with NIR-II laser irradiation. Moreover, hyperthermia-stimulated nitric oxide (NO) release in situ acted as a gas immunomodulator to effectively enhance blood perfusion and reprogram the TIME via multiple functions (e.g., decreasing PD-L1, repolarizing tumor-associated macrophages, and revitalizing cytotoxic T cells). Ultimately, the inhibition rate against 4T1 mouse mammary tumor model mediated by GNR-SNO@MMT plus NIR-II laser was 94.7% together with 2.4-fold CD8⁺ T cells infiltrated into tumors than that of the untreated counterpart.</p><p><strong>Conclusions: </strong>The engineered biomimetic nano-modulator of GNR-SNO@MMT provides an effective and novel photoimmunotherapy candidate against deep-sited solid tumors through immune reconfiguration via NO-involved nanomedicine and external NIR-II laser assistance.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"220"},"PeriodicalIF":10.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}