Journal of Nanobiotechnology最新文献

{"title":"Targeting circulating tumor cell‒neutrophil interactions: nanoengineered strategies for inhibiting cancer metastasis.","authors":"Yong Su, Mingjing Leng, Qingqing Yang, Wenbi Jiang, Gang Xiang, Ling Long, Xing Zhou","doi":"10.1186/s12951-025-03522-8","DOIUrl":"10.1186/s12951-025-03522-8","url":null,"abstract":"<p><p>Metastasis remains the leading cause of cancer-related mortality, with a persistently poor prognosis for metastatic cancer patients despite extensive therapeutic efforts. Circulating tumor cells (CTCs), which detach from primary tumors and enter the bloodstream, can establish distant metastatic sites. These CTCs often form heterotypic clusters with white blood cells, especially neutrophils, through various interaction mechanisms, including intercellular adhesion, cytokine secretion, protease release, and the formation of neutrophil extracellular traps (NETs). These interactions enhance CTCs survival, proliferation, invasion, and transendothelial migration while simultaneously remodeling premetastatic niches and the tumor microenvironment. Consequently, pharmacologically disrupting CTC‒neutrophil crosstalk represents a promising strategy to curb metastatic spread and improve clinical outcomes. Recent breakthroughs in nanotechnology-based drug delivery systems have shown considerable potential in antimetastatic therapies, offering significant advantages over conventional treatments, which are often associated with severe side effects and limited efficacy. This review systematically explores nanoengineered strategies targeting CTC‒neutrophil interactions, addresses the current limitations and outlines future directions for developing clinically translatable nanotherapeutics.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"449"},"PeriodicalIF":10.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317146","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":"Biosynthesized nanoparticles of Tibetan medicine mercuric sulfide preparation to promote endocytosis and realize drug crossing through blood brain barrier.","authors":"Wenjing Jia, Huilan Yue, Liying Liu, Luya Wang, Lin Zhang, Jihong Tao, Guoying Zhou, Lixin Wei, Hongxin Dong, Rinchen Dhondrup, Xiaohui Zhao","doi":"10.1186/s12951-025-03525-5","DOIUrl":"10.1186/s12951-025-03525-5","url":null,"abstract":"<p><p>β-HgS as the main component of Tibetan medicine Zuotai (ZT) is widely used in the treatment of central nervous system diseases. Although the synergism of HgS has been clinically verified for more than 2000 years, its synergetic mechanism is still an unsolved mystery and a huge challenge. Notably, we clearly and intuitively demonstrate that Zuotai or β-HgS is auto-synthesized by organisms into spherical HgS nanoparticles with protein corona, with an overall particle size of 30-195 nm and a core of HgS NPs of 5-7 nm. Further research showed that HgS NPs facilitated the transport of Oxiracetam (ORT), Memantine Hydrochloride (MH) and Entinostat (MS-275) across the blood-brain barrier (BBB), especially the brain accumulation of MS-275 increased by more than three times. Meanwhile, HgS NPs enhanced the effect of MS-275 on spatial learning and memory ability of APP/PS1 mice. Further studies confirmed that HgS NPs increased the permeability of the blood-brain barrier (BBB) by regulating endocytosis (Upregulation of caveolin, clathrin, and dynamin, downregulation P-gp) thereby facilitate the transport of drugs across BBB with more than threefold higher brain accumulation and long-lasting efficiency enhancement (4 days). Our findings reveal that these in vivo-generated HgS NPs provide an efficient, convenient, and biocompatible drug delivery platform for crossing the BBB. Importantly, our findings offer new hopes and ideas for in-depth research on highly valuable and mysterious metal preparations in classic Chinese and Tibetan medicine.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"445"},"PeriodicalIF":10.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310043","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":"BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma.","authors":"Li Ai, Zhijuan Liu, Ran Li, Ying Hu, Yongxia Li","doi":"10.1186/s12951-025-03496-7","DOIUrl":"10.1186/s12951-025-03496-7","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma, the most common type of non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths globally due to its high incidence and treatment difficulty. Despite recent advancements in treatment methods, the prognosis for patients with advanced disease remains poor. Studies have shown that targeting mitophagy, the selective clearance of damaged mitochondria, can influence the sensitivity of cancer cells to treatment.</p><p><strong>Methods: </strong>In this study, we designed and synthesized BPQDs@Lipo-YSA, a novel nanomaterial, aimed at specifically inducing mitophagy in lung adenocarcinoma cells. The nanomaterial was characterized using techniques such as transmission electron microscopy (TEM) and dynamic light scattering (DLS). The ability of BPQDs@Lipo-YSA to induce mitophagy was evaluated using Western blot, immunofluorescence, and flow cytometry. Additionally, in vitro and in vivo experiments were conducted to investigate the impact of BPQDs@Lipo-YSA on lung adenocarcinoma cells through the induction of immunogenic cell death (ICD).</p><p><strong>Results: </strong>Experimental results showed that BPQDs@Lipo-YSA effectively induced mitophagy in lung adenocarcinoma cells by activating the PRKN/AKT1 pathway. More importantly, this induction of mitophagy significantly enhanced the cytotoxic effect on lung adenocarcinoma cells. In animal models, BPQDs@Lipo-YSA, by inducing ICD, markedly inhibited tumor growth and extended survival.</p><p><strong>Conclusions: </strong>This study reveals the potential value of BPQDs@Lipo-YSA in lung adenocarcinoma treatment through the induction of mitophagy and ICD. This finding provides theoretical and technical support for the development of new therapeutic strategies for lung adenocarcinoma.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"446"},"PeriodicalIF":10.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310044","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":"An immune activator encapsulating PD-L1 siRNA for augmented immune checkpoint blockade immunotherapy through Zn²⁺ overload triggered pyroptosis.","authors":"Liming Gong, Yanhong Liu, Jing Feng, Congcong Xiao, Chenfei Liu, Bohan Chen, Liqing Chen, Mingji Jin, Youyan Guan, Zhonggao Gao, Wei Huang","doi":"10.1186/s12951-025-03521-9","DOIUrl":"10.1186/s12951-025-03521-9","url":null,"abstract":"<p><p>Breast cancer as a \"cold\" tumor presents an immunosuppressive microenvironment and inferior T-lymphocyte infiltration, leading to poor efficacy of immune checkpoint blockade (ICB) therapies. It is urgent to develop new effective combination treatment strategies. Pyroptosis is an inflammatory form of programmed cell death mediated by Caspase-1/GSDMD pathway, which can cause immunogenic cell death (ICD) and boost the immunogenicity of tumor. In this study, an immune activator (siRNA^PD-L1@HA-ZIF-8) was proposed based on metal-organic framework (ZIF-8) nanosystem carrying Zn²⁺ and PD-L1 siRNA to improve anti-tumor immunotherapy through evoking pyroptosis combined with immune checkpoint blockade. We found that siRNA^PD-L1@HA-ZIF-8 could disintegrate under low pH and release massive amounts of Zn²⁺, leading to elevated intracellular osmolarity and ROS, eventually resulting in pyroptosis. Zn²⁺ overload-triggered pyroptosis caused ICD effect and promoted the maturation of dendritic cells and infiltration of T-lymphocytes, which reprogramed the immunoecology of tumor from \"cold\" to \"hot\" state. Meanwhile, the co-delivered PD-L1 siRNA decreased the expression of PD-L1 protein on the tumor surface, relieving immune evasion and recovering the recognition and killing ability of cytotoxic T-lymphocytes, further boosting the immune response. This research not only confirmed the potential of ZIF-8 intrinsically as an immune activator that induces pyroptosis in combination with encapsulated PD-L1 siRNA-mediated ICB therapy for the first time, but also adequately revealed the immune responses mechanism by multiple techniques. This study will provide new strategies for pyroptosis-mediated treatments for augmented anti-tumor immunotherapy and greatly inspire the further development of immune activators based on Zn²⁺ overload-triggered pyroptotic pathway.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"447"},"PeriodicalIF":10.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310042","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":"A self-adhesive hierarchical nanofiber patch for dynamic and multistage management of full-thickness cutaneous wounds.","authors":"Lihuang Wu, Yuqi Wang, Xinyue Zhao, Tingting Zhao, Junhua Li, Yi Kuang, Yiyan He, Shengxiang Yang, Zhongwei Gu, Hongli Mao","doi":"10.1186/s12951-025-03513-9","DOIUrl":"10.1186/s12951-025-03513-9","url":null,"abstract":"<p><p>Full-thickness cutaneous wounds pose a significant threat to global health due to their complex healing demands. Standard clinical wound dressings often fall short in providing the adaptability and functionality required for the entire healing process. While hierarchically engineered nanofiber dressings have shown advancement in wound management, challenges such as material compatibility and interfacial bonding during their design have limited both manufacturing and therapeutic outcomes. This study introduces a self-adhesive hierarchical nanofiber (SAHN) patch designed to provide a comprehensive and dynamic approach to wound care. The SAHN patch strategically integrates synthetic biodegradable poly(ester carbonate) with natural bioactive components, forming a seamless dual-layer system that offers both immediate protection and sustained bioactivity to support tissue regeneration. In vitro and in vivo studies demonstrate the patch's superior interlayer adhesion, soft tissue adhesion, controlled degradation, and robust antibacterial capabilities. These features collectively safeguard the wound microenvironment, facilitate hemostasis, manage inflammation, and accelerate wound closure. Our findings highlight the transformative potential of the SAHN patch in improving traditional wound care, overcoming the manufacturing challenges associated with hierarchical nanofiber dressings, and offering a promising solution for dynamic and multistage management of full-thickness cutaneous wounds that aligns with the natural progression of tissue repair.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"448"},"PeriodicalIF":10.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310032","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":"Coptis chinensis-derived extracellular vesicle-like nanoparticles delivered miRNA-5106 suppresses NETs by restoring zinc homeostasis to alleviate colitis.","authors":"Yi Yang, Lanmengxi Yang, Haiyi Deng, Yuheng Liu, Junwei Wu, Yilin Yang, Jin Su, Shiyu Su, Junhao Xu, Jie Wei, Xiaoyan Deng, Yujin Wu, Yao Liao, Lifu Wang","doi":"10.1186/s12951-025-03466-z","DOIUrl":"10.1186/s12951-025-03466-z","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a chronic disorder marked by persistent inflammation and damage to the intestinal mucosa. Despite significant advances in treatment, there remains an unmet need for more effective and safer therapeutic strategies.</p><p><strong>Results: </strong>In this study, we isolated and characterized extracellular vesicle-like nanoparticles (ELNs) derived from Coptis chinensis (Cc-ELNs) and evaluated their therapeutic potential in IBD. Intraperitoneal administration of Cc-ELNs in dextran sulfate sodium (DSS)-induced colitis mice demonstrated selective targeting of inflamed intestinal regions. Cc-ELNs significantly alleviated colitis by reducing neutrophil recruitment and inhibiting the formation of neutrophil extracellular traps (NETs). Furthermore, by suppressing NET formation, Cc-ELNs mitigated pyroptosis in intestinal epithelial cells (IECs) and promoted the proliferation of both IECs and intestinal stem cells (ISCs). Mechanistically, Cc-ELNs delivered miR-5106, which downregulated Slc39a2 expression, thereby restoring zinc homeostasis in neutrophils and reducing NET formation.</p><p><strong>Conclusions: </strong>These findings establish Cc-ELNs as a novel, natural, and effective therapeutic candidate for IBD, highlighting the potential of plant-derived nanoparticle-based therapies.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"444"},"PeriodicalIF":10.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293891","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":"Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy.","authors":"Wenjing Xiao, Xiao Yang, Mengzhen Wang, Zeyu Jiang, Heyi Zhang, Mengqing Gong, Lin Zhao, Jibin Song, Qinrui Fu","doi":"10.1186/s12951-025-03531-7","DOIUrl":"10.1186/s12951-025-03531-7","url":null,"abstract":"<p><p>The standard treatment for various types of cancers typically involves the combination of concurrent localized radiotherapy and systemic chemotherapy. However, no treatment options have been reported that utilize chemotherapy cascade-enhanced radiotherapy. In this study, we report a core-satellite nanomedicine designed to enhance radiotherapeutic effects through a cascade mechanism by triggering the release of a potent chemotherapeutic agent in response to trypsin. We synthesized a functional enzyme-sequential responsive nanomedicine, DOX@Gel-DEVD-AuNR, which consists of gelatin nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX). These nanoparticles are covalently linked to gold nanorods (AuNR) via a caspase-3 specific DEVD peptide substrate. Upon trypsin activation, the DOX@Gel-DEVD-AuNR formulation releases DOX, thereby enhancing chemotherapy efficacy against tumors. Simultaneously, it activates caspase-3, inducing the aggregation of AuNRs, which in turn activates a near-infrared-II photoacoustic signal. This signal is crucial for determining the optimal timing for X-ray irradiation. The resulting large-size AuNRs aggregates promote their accumulation within tumors by preventing the migration and backflow of AuNRs, thereby improving radiotherapeutic effects. Consequently, when combined with image-guided X-ray irradiation, DOX@Gel-DEVD-AuNR induces significant cytotoxicity in cancer cells and effectively inhibits tumor growth. Our study underscores the potential application of enzyme catalysis-mediated chemistry in activating nanomedicine for activatable image-guided chemotherapy cascade-enhanced radiotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"440"},"PeriodicalIF":10.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293892","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":"Nanoscale engineered exosomes for dual delivery of Sirtuin3 and insulin to ignite mitochondrial recovery in myocardial ischemia-reperfusion.","authors":"Jiaxin Yang, Xinyi Yun, Weihan Zheng, Huihui Zhang, Zi Yan, Youyu Chen, Wanting Xue, Siqi Mi, Ziyue Li, Hanxiao Sun, Guozhi Xiao, Zhenning Dai, Shiyu Li, Wenhua Huang","doi":"10.1186/s12951-025-03474-z","DOIUrl":"10.1186/s12951-025-03474-z","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction remains a leading cause of mortality, with ischemia-reperfusion (I/R) injury causing severe myocardial damage through mitochondrial dysfunction. While mesenchymal stem cell-derived exosomes (MSC-Exo) show therapeutic potential, their limited targeting and insufficient mitochondrial protection restrict clinical application.</p><p><strong>Results: </strong>We developed a novel engineered exosome platform (Exo-I-S) using an IRES-driven bicistronic plasmid to co-load Sirtuin3 (SIRT3) and GPI-Insulin, aiming to enhance targeting efficiency and mitochondrial protection. The platform was evaluated in both in vitro and in vivo models of myocardial I/R injury. In vitro, Exo-I-S achieved faster cellular uptake, improved mitochondrial function, and reduced oxidative stress in H9c2 cells. The platform activated PI3K/AKT signaling, enhanced Glut4 translocation, and improved mitochondrial respiratory capacity. In a rat I/R injury model, Exo-I-S significantly reduced infarction size, improved cardiac function, and enhanced glucose metabolism, with superior therapeutic outcomes compared to unmodified exosomes.</p><p><strong>Conclusions: </strong>The dual functionality of Exo-I-S, combining insulin-mediated targeting with SIRT3-driven mitochondrial protection, provides a promising strategy for I/R injury treatment. Future studies should focus on optimizing targeting specificity and developing sustained release mechanisms to enhance clinical applicability.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"439"},"PeriodicalIF":10.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293894","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":"Overcoming acquired immunotherapy resistance in non-small cell lung cancer using ginsenoside Rb1-loaded, peptide-enhanced exosome delivery systems.","authors":"Xiangyuan Jin, Tanghesi Wuyun, Yu Zhang, Xiaohong Wang, Ling Zhao","doi":"10.1186/s12951-025-03456-1","DOIUrl":"10.1186/s12951-025-03456-1","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a major global health challenge, with limited therapeutic success due to drug resistance and the immunosuppressive tumor microenvironment (TME). This study explores a novel strategy to overcome acquired resistance to immunotherapy in phosphoinositide 3-kinase (PI3K)-mutated NSCLC. Tumor-derived exosomes (T-exo) were modified with the tumor-targeting peptide TMTP1 and loaded with Ginsenoside Rb1 (Rb1) via electroporation to develop peptide-modified Rb1@T-exo. This innovative delivery system demonstrated enhanced tumor-targeting ability and improved stability and bioavailability of Rb1. Both in vitro and in vivo experiments revealed that Rb1@T-exo effectively suppressed tumor growth and metastasis, significantly inhibited the PI3K/AKT/mTOR signaling pathway, and remodeled the immune microenvironment by promoting M1 macrophage polarization and enhancing CD8⁺ T cell proliferation and cytotoxicity. Transcriptomic and bioinformatic analyses identified key differentially expressed genes (DEGs) and pathways associated with resistance reversal, including the PI3K/AKT/mTOR and PD-1/PD-L1 pathways. Moreover, Rb1@T-exo synergized with immune checkpoint blockade therapy, demonstrating potential as a dual therapeutic approach. This study highlights the potential of peptide-modified Rb1@T-exo as a targeted therapeutic platform for overcoming immunotherapy resistance in PI3K-mutated NSCLC and provides a promising direction for future anti-tumor therapies.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"443"},"PeriodicalIF":10.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293895","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":"Transdermal delivery of CRISPR/Cas9-mediated melanoma gene therapy via polyamines-modified thermosensitive hydrogels.","authors":"Meng Li, Songli Zhou, Suqin Zhang, Xingyu Xie, Junqi Nie, Qi Wang, Lixin Ma, Yibin Cheng, Jingwen Luo","doi":"10.1186/s12951-025-03523-7","DOIUrl":"10.1186/s12951-025-03523-7","url":null,"abstract":"<p><p>The main obstacles to the clinical application of the CRISPR/Cas9 system are off-target effects and low delivery efficiency. There is an urgent need to develop new delivery strategies and technologies. Three types of in situ injectable hydrogels with different electrical properties were created to find the most secure and efficient sustained-release drug delivery system. After in vitro and in vivo comparisons, we found that the positively charged hydrogels had higher cellular uptake, stronger gene editing efficiency, greater cytotoxicity, longer tumor accumulation, and better anti-tumor efficacy than negatively charged and neutral hydrogels. We designed single guide RNA targeting the Y-box binding protein 1 (YB-1) gene and then used it to create a ribonucleoprotein complex with Cas9 protein. Doxorubicin was co-encapsulated into this positively charged hydrogel to create a co-delivery system. By knocking down YB-1, the expression of YB-1 was reduced, inhibiting the growth and migration of melanoma cells. The strategy of combining YB-1 gene editing and intratumoral injection enhanced the therapeutic effect of doxorubicin while reducing side effects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"441"},"PeriodicalIF":10.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293896","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}