Wenrui Zhao, Xiaolin Tang, Yucui Qin, Xiaochang Wang, Keqing Zhong, Ningqiang Gong, Tao Li
{"title":"Nanomaterials Application for STING Pathway-Based Tumor Immunotherapy.","authors":"Wenrui Zhao, Xiaolin Tang, Yucui Qin, Xiaochang Wang, Keqing Zhong, Ningqiang Gong, Tao Li","doi":"10.2147/IJN.S535460","DOIUrl":"10.2147/IJN.S535460","url":null,"abstract":"<p><p>The STING pathway has emerged as a therapeutic target in tumor immunotherapy due to its ability to induce interferon responses, enhance antigen presentation and activate T cells. Despite its therapeutic potential, STING pathway-based tumor immunotherapy has been limited by challenges in poor cellular delivery, rapid degradation of STING agonists, and potential systemic toxicity. Recently, advancements in nanotechnology have tried to overcome these limitations by providing platforms for more accurate and efficient targeted delivery of agonists, more moderate sustained STING pathway activation, and more efficient immune presentation and anti-tumor immune response. This review systematically examines the application of nanomaterials in STING pathway-based tumor immunotherapy, focusing on three principal strategies: enhancing tumor vaccine efficacy, modulating the tumor microenvironment, and improving T cell mediated tumor immunotherapy. The challenges to clinical translation, including clinical trial research updates, regulatory hurdles, and biosafety considerations, are also discussed. Overall, STING pathway-based nanomaterials offer promising potential for clinical translation in tumor immunotherapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10771-10793"},"PeriodicalIF":6.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evi Sulastri, Maya Nurul Rahma, Yedi Herdiana, Khaled M Elamin, Ahmed Fouad Abdelwahab Mohammed, Safwat A Mahmoud, Nasrul Wathoni
{"title":"Enhancing Antifungal Efficacy and Stability of Nystatin Liposomes Through Chitosan and Alginate Layer-by-Layer Coating: In vitro Studies Against <i>Candida albicans</i>.","authors":"Evi Sulastri, Maya Nurul Rahma, Yedi Herdiana, Khaled M Elamin, Ahmed Fouad Abdelwahab Mohammed, Safwat A Mahmoud, Nasrul Wathoni","doi":"10.2147/IJN.S526763","DOIUrl":"10.2147/IJN.S526763","url":null,"abstract":"<p><strong>Background: </strong>Candidiasis, predominantly caused by <i>Candida albicans</i>, poses a significant global health challenge, especially in tropical regions. Nystatin is a potent antifungal agent that is hindered by its low solubility and permeability, limiting its clinical efficacy.</p><p><strong>Methods: </strong>This study aimed to investigate the potential of a layer-by-layer (LBL) coating system, employing chitosan and alginate, to improve the stability, entrapment efficiency (%EE), and antifungal efficacy of nystatin-loaded liposomes against Candida albicans. Nystatin liposomes were synthesized via a thin-film hydration method and subsequently coated with varying ratios of chitosan and alginate using the LBL technique. The optimized formulations were characterized in terms of their particle size, zeta potential, %EE, and morphology. Furthermore, in vitro release dynamics, antifungal activity through Minimum Inhibitory Concentration (MIC) assays, and stability tests at 4°C were conducted.</p><p><strong>Results: </strong>The optimal formulation, designated as NA7-Ch3-Nys-Lip, exhibited a significant improvement in %EE (61.61 ± 1.60% to 83.77 ± 2.00%), enhanced antifungal activity (MIC value of 0.732 µg/mL), and superior stability compared to uncoated liposomes. The LBL system facilitated controlled drug release and maintained desirable particle characteristics under prolonged storage conditions.</p><p><strong>Conclusion: </strong>This study successfully demonstrated that LBL-coated nystatin liposomes significantly enhanced the antifungal activity, stability, and delivery efficiency of the drug. This novel formulation strategy offers a promising approach to overcome the limitations of conventional antifungal therapies, potentially improving the treatment of fungal infections.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10739-10750"},"PeriodicalIF":6.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hang Ning, Xinyu Huang, Na Deng, Xiaoyuan Lin, Ling Zheng, Ying Zhu, Yin Xu
{"title":"Plant-Derived Exosome-Like Nanovesicles: A Novel Strategy for Targeted Oral Therapy in Ulcerative Colitis.","authors":"Hang Ning, Xinyu Huang, Na Deng, Xiaoyuan Lin, Ling Zheng, Ying Zhu, Yin Xu","doi":"10.2147/IJN.S536056","DOIUrl":"10.2147/IJN.S536056","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease, the incidence of which continues to rise globally, and existing therapeutic options are limited by low drug bioavailability and systemic side effects. In this study, we systematically investigated the challenges of the special gastrointestinal environment of UC patients for oral drug delivery, such as extreme pH, degradation by digestive enzymes, metabolism of intestinal flora and obstruction of the intestinal mucosal barrier, and summarized the potential of plant-derived Exosome-like Nanovesicles (PELNs) as a novel delivery system. PELNs are produced by plant cells and mainly consist of proteins, RNA, lipids and plant active molecules. Animal and cell experiments have shown that they can treat UC through the regulation of the intestinal bacterial flora, the inhibition of inflammatory pathways, and the promotion of mucosal repair, etc. On the other hand, their small particle size (30-500 nm), negative charge and lipid bilayer structure enable them to penetrate the intestinal mucus layer, tolerate extreme pH and enzymatic degradation, and adhere to intestinal epithelial cells through electrostatic interactions, thus possessing advantages such as low immunogenicity, high stability and natural targeting. Furthermore, the engineering modification of PELNs can significantly enhance targeting and therapeutic efficacy, such as surface modification or drug loading. Future research should focus on the systematic characterization, safety validation, large-scale production and multimodal combination therapy of PELNs in order to promote their clinical translation, which not only provides an efficient delivery platform for the treatment of UC, but also opens up a new pathway for the development of natural medicines.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10595-10611"},"PeriodicalIF":6.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phytochemicals in Bone Therapy: Exploring Natural Alternatives for Bone Health.","authors":"Hiba Abdelnabi, Sahar Mohsin","doi":"10.2147/IJN.S524695","DOIUrl":"10.2147/IJN.S524695","url":null,"abstract":"<p><p>Bone diseases such as osteoporosis and osteoarthritis are increasingly prevalent, particularly in aging populations. While conventional treatments, including synthetic drugs and mineral supplements, are effective yet often associated with side effects and long-term economic burdens. Active compounds derived from nature, \"Phytochemicals\" have garnered attention due to their potential to provide safer and more sustainable alternative therapeutic options. However, due to their complex structure and poor pharmacokinetics, their clinical applications are limited. Nano-drug delivery systems address these limitations by developing phytochemical-based nanocarriers, which enable targeted delivery, protect active compounds, and enhance both pharmacokinetics and pharmacodynamics. Given the limitations of synthetic treatments, there is growing interest in exploring phytochemicals and plants and herbal extracts to support bone health. This review focuses on nano-phytochemical approaches for bone therapy, outlining key phytochemicals, their natural sources, nanoformulations, and mechanisms of action. It also evaluates current commercial supplements and highlights the challenges and future directions for clinical translation of nano-phytomedicine in bone health management.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10831-10855"},"PeriodicalIF":6.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Progress in Peptide-Based Fluorescent Probes Biomedical Applications: A Review.","authors":"Xue Zhong, Yuanlong Xie, Yuen Chen, Yushen Lu, Mingming Hou","doi":"10.2147/IJN.S529323","DOIUrl":"10.2147/IJN.S529323","url":null,"abstract":"<p><p>Peptide-based fluorescent probes have found widespread applications in biomedical research, including bio-imaging, disease diagnosis, drug discovery, and image-guided surgery. Their favorable properties-such as small molecular size, low toxicity, minimal immunogenicity, and high targeting specificity-have contributed to their growing utility in both basic research and translational medicine. This review provides a comprehensive overview of recent advances in peptide-based fluorescent probes, emphasizing design strategies, biological targets, and diverse functional applications. Key areas of focus include the integration of molecular targeting with imaging capabilities, the emergence of multimodal imaging techniques, and the development of activatable probes responsive to specific biological stimuli. Applications are discussed in the context of tumor cell membrane recognition, subcellular organelle targeting, non-cancer disease diagnosis, and detection of both metal ions and non-metal ions. Notably, responsive probes for reactive oxygen species (ROS) and other biologically relevant non-metal ions are also highlighted, underscoring their diagnostic and therapeutic potential. The review also addresses key limitations-such as poor in vivo stability, limited targeting accuracy, and delivery efficiency-and outlines future directions including smart peptide probe platforms, self-reporting systems, and high-throughput screening based on peptide libraries to accelerate next-generation probe development.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10751-10770"},"PeriodicalIF":6.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Zhang, Weili Guan, Ting Guo, Yingchun Zhang, Chulan Gong, Rui Ye, Dan Fang, Jinxi Zuo, Xiaojin Lin, Yuting Fan, Zailing Yang, Dan Liang, Tao Shen, Liang Chen, Xing Zhao
{"title":"Comparison of the Cytotoxicity, Internalization and Anti-Cancer Drug Delivery Efficacy of Nature Killer Cell Derived Nanovesicles and Extracellular Vesicles.","authors":"Jing Zhang, Weili Guan, Ting Guo, Yingchun Zhang, Chulan Gong, Rui Ye, Dan Fang, Jinxi Zuo, Xiaojin Lin, Yuting Fan, Zailing Yang, Dan Liang, Tao Shen, Liang Chen, Xing Zhao","doi":"10.2147/IJN.S527756","DOIUrl":"10.2147/IJN.S527756","url":null,"abstract":"<p><strong>Purpose: </strong>Natural killer (NK) cell-derived extracellular vesicles (NK-EVs) have garnered significant research interest in the field of tumor immunotherapy. However, the large-scale production of NK-EVs remains a major challenge, limiting their clinical application. This study aims to develop a simple and efficient method for the preparation of NK cell-derived nanovesicles (NK-NVs) and to evaluate their cytotoxicity and drug delivery potential.</p><p><strong>Methods: </strong>In this study, we efficiently produced large quantities of NK-NVs by extruding NK cells. We conducted comprehensive characterization and protein profiling analyses of NK cells, NK-EVs, and NK-NVs. The cytotoxicity and cellular uptake of NK-NVs were evaluated, and the internalization mechanism was explored. To assess the drug delivery capability, doxorubicin (DOX) was loaded into NK-NVs (NK-NVs-DOX) using various loading strategies, including co-incubation, sonication, extrusion, and electroporation. We thoroughly evaluated the drug loading efficiency, particle size, stability, and cytotoxicity of NK-NVs-DOX.</p><p><strong>Results: </strong>Extrusion-derived NK-NVs exhibited a remarkable 402.18-fold increase in particle yield and a 325.76-fold enhancement in protein yield compared to ultracentrifugation-isolated NK-EVs, while maintaining comparable morphology and EV-specific markers (Alix, TSG101, CD9). Functionally, NK-NVs induced delayed cytotoxicity against cancer cells via caveolin-mediated endocytosis, selectively sparing normal cells. Proteomic analysis revealed that NK-NVs shared 7,366 proteins with NK cells, surpassing the 5,326 proteins found in NK-EVs. Furthermore, extrusion-optimized NK-NVs-DOX demonstrated pH-sensitive drug release (30% higher at pH 5.5), significantly enhanced anti-cancer effects across four cancer cell lines, and stable drug retention for up to 28 days at 4°C, highlighting their promising therapeutic potential.</p><p><strong>Conclusion: </strong>Extrusion-derived NK-NVs offer a low-cost, rapid, and high-yield production method while selectively inducing cytotoxicity in cancer cells. Their pH-sensitive drug release enhances drug loading stability. These advantages establish NK-NVs as a promising and scalable platform for tumor immunotherapy and drug delivery with significant clinical potential.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10683-10700"},"PeriodicalIF":6.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yadong Liu, Huiyan Lv, Yaodong Chen, Shazhou Ye, Zhong Zheng, Lei Chen, Zejun Yan, Xingyi Li
{"title":"Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA Nanoparticles for Highly Effective Combination of Chemodynamic, Photodynamic and Photothermal Therapies Against Bladder Cancer.","authors":"Yadong Liu, Huiyan Lv, Yaodong Chen, Shazhou Ye, Zhong Zheng, Lei Chen, Zejun Yan, Xingyi Li","doi":"10.2147/IJN.S534840","DOIUrl":"10.2147/IJN.S534840","url":null,"abstract":"<p><strong>Background: </strong>Due to the complex structure and variable microenvironment in the progression of bladder cancer, the efficacy of traditional treatment methods such as surgery and chemotherapy is limited. Tumor residual, recurrence and metastasis are still difficult to treat. The integration of diagnosis and treatment based on nanoparticles can offer the potential for precise tumor localization and real-time therapeutic monitoring. Photodynamic therapy (PDT), which generates reactive oxygen species (ROS) under laser irradiation, can be effectively combined with photothermal therapy (PTT) and chemodynamic therapy (CDT) to target non-muscle-invasive bladder tumors. In this study, Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA nanoparticles with photoacoustic (PA) imaging capabilities were utilized to explore their potential for precise intraoperative tumor identification and multimodal therapy.</p><p><strong>Methods: </strong>The generation of ROS was detected to evaluate the potential of PDT and copper ion-induced CDT. Additionally, the PA imaging capability and biosafety of the nanoparticles were systematically evaluated. Finally, the anti-tumor efficacy of Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA-mediated CDT/PDT/PTT and the underlying mechanisms were assessed in vitro and in vivo.</p><p><strong>Results: </strong>Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA could implement the CDT effect through a Cu<sup>+</sup>-induced Fenton-like reaction and substantial consumption of glutathione (GSH). Besides, Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA could execute NIR-I-triggered PDT by generating <sup>1</sup>O<sub>2</sub> and thermal images showed that Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA has the potential to perform PTT through light-heat energy conversion. Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA possessed dose-dependent PA signal transduction ability. Without laser exposure, Cu<sub>2</sub>(OH)PO<sub>4</sub>@PAA weakened cell viability, induced apoptosis, and suppressed epithelial-mesenchymal transition (EMT) by exhibiting the CDT effect alone. However, after the introduction of PDT and/or PTT, the above anti-tumor effects were significantly enhanced.</p><p><strong>Conclusion: </strong>This study systematically explores the combined anti-cancer mechanisms from the perspective of epithelial-mesenchymal transition, providing a theoretical and technical foundation for bladder cancer treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10701-10719"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gold/Prussian Blue-Based Nanocomposites with Dual Nanozyme Activities Exert a Synergistic Effect of Starvation Therapy and Sonodynamic Therapy in the Treatment of Liver Cancer.","authors":"Shengnan Huang, Chengzhi Song, Tengyue Zhao, Yefei Yang, Zhiwei Yao, Shaofeng Duan, Wanyi Chen, Lixian Li, Xiaogang Hu, Chunming Li, Yurong Hu","doi":"10.2147/IJN.S490343","DOIUrl":"10.2147/IJN.S490343","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop a composite nanozyme system (Au/PB-Ce6-HA) based on gold nanoparticles (AuNPs) and Prussian blue nanoparticles (PBNPs) to combat tumor hypoxia and insufficient endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) deficiency, thus enhancing the efficacy of sonodynamic therapy (SDT) and starvation therapy for liver cancer.</p><p><strong>Methods: </strong>The Au/PB-Ce6-HA system was constructed by in situ embedding AuNPs on PBNPs, loading the sonosensitizer Chlorin e6 (Ce6), and surface-coating with thiolated hyaluronic acid (HA-SH). The system was evaluated both in vitro and in vivo to assess its ability to catalyze glucose to generate H<sub>2</sub>O<sub>2</sub>, decompose H<sub>2</sub>O<sub>2</sub> to produce oxygen, and generate highly toxic reactive oxygen species (ROS) under ultrasound irradiation.</p><p><strong>Results: </strong>The Au/PB-Ce6-HA nanozymes demonstrated high catalytic activity, thus significantly improving SDT and starvation therapy. Specifically, the system effectively deprived tumors of their energy supply by generating H<sub>2</sub>O<sub>2</sub>, while simultaneously producing oxygen to enhance cytotoxic ROS generation under ultrasound irradiation. Both in vivo and in vitro studies further demonstrated a synergistic effect in inhibiting tumor growth while enhancing therapeutic efficacy.</p><p><strong>Conclusion: </strong>An intelligent composite nanomaterial was successfully developed, combining starvation therapy and sonodynamic therapy to significantly enhance the treatment of liver cancer. The Au/PB-Ce6-HA nanozyme system demonstrated excellent synergy in both in vitro and in vivo settings, offering a promising strategy for cancer therapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10721-10737"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zheng Zhang, Xiang Sun, Zihan Gao, Xin Lv, Hui Jia, Bin Huang, Chengwan Xia, Xudong Yang
{"title":"Prussian Blue Nanoparticle-Induced Alteration of the Polarization State of Tumor-Associated Macrophages as a Substantial Antitumor Mechanism Against Oral Squamous Cell Carcinoma (OSCC).","authors":"Zheng Zhang, Xiang Sun, Zihan Gao, Xin Lv, Hui Jia, Bin Huang, Chengwan Xia, Xudong Yang","doi":"10.2147/IJN.S528763","DOIUrl":"10.2147/IJN.S528763","url":null,"abstract":"<p><strong>Introduction: </strong>Oral squamous cell carcinoma (OSCC) has a poor prognosis due to its immunosuppressive tumor microenvironment (TME), in which tumor-associated macrophages (TAMs) play a pivotal role in promoting disease progression and therapeutic resistance. This study examines whether Prussian blue nanoparticles (PB NPs) could reprogram TAMs and block tumor-stroma communication in OSCC.</p><p><strong>Methods: </strong>PB NPs were synthesized using polyvinylpyrrolidone-assisted coprecipitation and characterized by transmission electron microscopy, dynamic light scattering, and UV-Vis spectroscopy. In vitro, their effects on macrophage polarization were assessed via immunofluorescence, Western blotting (CD206/CD86), and ELISA (TGF-β1/IL-6/TNF-α). The impact on OSCC-macrophage interaction was evaluated using CCK-8 assays, transwell co-culture systems with conditioned media. In vivo, xenograft-bearing mice were used to assess PB NP effects on OSCC-TAM crosstalk. Tumor growth, Ki67 proliferation index, and TAM phenotypes (CD206<sup>+</sup>/CD86<sup>+</sup>) were analyzed. Systemic biocompatibility was further assessed through CCK-8 in vitro and hematological profiling and histopathological examination in vivo.</p><p><strong>Results: </strong>PB NPs (diameter 57.43 ± 22.25 nm; zeta potential -17.36mV) were successfully made and showed good biocompatibility in vitro and in vivo. In vitro, they shifted M2 TAMs toward anti-tumor M1 phenotypes, reducing CD206 and TGF-β1 while increasing CD86 and pro-inflammatory cytokines (IL-6, TNF-α). This change disrupted OSCC-TAM communication, limiting tumor growth and migration. In vivo, PB NPs reduced tumor volume, lowered the Ki67<sup>+</sup> cell ratio, and increased the intratumoral M1/M2 macrophage ratio.</p><p><strong>Conclusion: </strong>Prussian blue nanoparticles effectively modulate the immunosuppressive TME in OSCC by shifting TAM polarization from the pro-tumor M2 phenotype to the anti-tumor M1 phenotype, thereby interrupting critical tumor-stroma interactions. Given their intrinsic immunomodulatory properties and favorable biosafety profile, PB NPs represent a promising and safe therapeutic strategy targeting the TME in OSCC.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10667-10681"},"PeriodicalIF":6.5,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karkaz M Thalij, Huay Woon You, Kiran Balasaheb Aher, Girija Balasaheb Bhavar, Smita Tukaram Kumbhar, Mohammad Habeeb
{"title":"Advances in Lipid-Based Nanomedicine: Pathway Specific siRNA Therapy and Optimizing Delivery for Hepatocellular Carcinoma.","authors":"Karkaz M Thalij, Huay Woon You, Kiran Balasaheb Aher, Girija Balasaheb Bhavar, Smita Tukaram Kumbhar, Mohammad Habeeb","doi":"10.2147/IJN.S532246","DOIUrl":"10.2147/IJN.S532246","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a major global health issue, ranking as the sixth most common cancer and a leading cause of cancer-related deaths worldwide. Risk factors for HCC include chronic hepatitis B and C, obesity, alcohol abuse, diabetes, and metabolic disorders. Current treatments, such as surgery, transplantation, and chemotherapy, are often ineffective in advanced stages due to tumor resistance and the inability to target key oncogenic pathways. Recent advances in small interfering RNA (siRNA) therapy offer a promising solution to silence these pathways and hinder tumor progression. Nanoparticles, especially lipid-based nanoparticles (LNPs) like liposomes, solid lipid nanoparticles, exosomes etc. have emerged as an effective platform for siRNA delivery. LNPs provide critical advantages, including protection of siRNA from enzymatic degradation, improved cellular uptake, and precise tumor targeting through functionalization strategies. Compared to polymeric and metallic nanocarriers, LNPs demonstrate superior biocompatibility, biodegradability, and safety profiles. Furthermore, their ability to exploit natural mechanisms, such as apolipoprotein E (ApoE)-mediated uptake via low-density lipoprotein receptors on hepatocytes, enhances liver-specific delivery. This review explores advancements in siRNA therapeutics for HCC, highlighting nanoparticle-based delivery, cell signaling targets, and synthesis strategies. It also examines AI's role in optimizing siRNA design, formulation, and personalized treatment. These innovations enhance pathway-specific therapies, advancing clinical translation and improving HCC outcomes.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10541-10566"},"PeriodicalIF":6.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}