International Journal of Nanomedicine最新文献

{"title":"Biomaterials Promote the Regression of Atherosclerotic Plaque by Regulating Cell Behavior.","authors":"Chunyan Wang, Chao Sun, Xiujuan Wu, Ziyan Ding, Kangding Liu, Jie Cao","doi":"10.2147/IJN.S574592","DOIUrl":"https://doi.org/10.2147/IJN.S574592","url":null,"abstract":"<p><p>Atherosclerosis is characterized by the deposition of lipid within arterial walls, precipitating the initiation and progression of atherosclerotic lesions. Over time, these plaques enlarge and rupture, initiating thrombosis cascades that pose significant risks to patient safety. Conventional therapies, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (eg, statins) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, predominantly target lipid reduction while overlooking the intricate microenvironment within atherosclerotic plaque. Statins possess limited lipid-lowering efficacy and may even exhibit insensitivity or intolerance in patients. While PCSK9 inhibitors, as adjuvant therapy, demonstrate potent lipid-lowering effects, they fail to further stabilize vulnerable plaques. In contrast, biomaterials have emerged as pivotal tools for addressing unstable plaques. By restoring endothelial cell (EC) function, inhibiting neutrophil activation, modulating macrophage behavior, and preventing the phenotypic transformation of smooth muscle cells, biomaterials effectively promote plaque regression. This review explores the pathogenesis of atherosclerosis and highlights recent advancements in biomaterial-based therapies for vulnerable plaques, aiming to offer novel insights and solutions to this pressing global health challenge.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"574592"},"PeriodicalIF":6.5,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837621","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":"Heparin-Conjugated Silver Nanoparticles via Amide Chemistry for Selective Targeting of Triple-Negative Breast Cancer and Pathogenic Fungi.","authors":"Jayshree H Ahire, Qi Wang, Yongping Bao, Isabelle S R Storer, Stefan Bidula, Gary Rowley, Jason C Crack","doi":"10.2147/IJN.S576538","DOIUrl":"https://doi.org/10.2147/IJN.S576538","url":null,"abstract":"<p><strong>Background: </strong>Heparin, a polydisperse glycosaminoglycan, is well-known for its anticoagulant activity and clinical use in preventing venous thromboembolism. In addition to coagulation, heparin and its derivatives have shown therapeutic potential in cancer and infectious, inflammatory, and neurodegenerative diseases. This study aimed to develop and evaluate heparin-capped AgNPs (hep-AgNPs) as multifunctional nanotherapeutics with selective cytotoxicity, antibacterial, and antifungal activity.</p><p><strong>Methods: </strong>Heparin was covalently conjugated to cysteamine-terminated silver nanoparticles via MES-buffer-mediated amide coupling, providing a mild, aqueous alternative to conventional DMF-based methods. The nanoparticles were characterised by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analyses. The colloidal stability was assessed over a broad range of pH values. The biological performance of hep-AgNPs was evaluated in vitro against a triple-negative breast cancer (TNBC) cell line (MDA-MB-231), a double-positive cell line (MCF-7), and normal breast cells (MCF-10A), and microbial strains, including <i>Salmonella typhimurium, E. coli, Aspergillus fumigatus</i>, and <i>Candida albicans</i>.</p><p><strong>Results: </strong>The synthesised hep-AgNPs exhibited high yield, effective heparin surface functionalization, and excellent colloidal stability at physiological pH, with stability systematically assessed across a broad pH range. Hep-AgNPs demonstrated time and concentration-dependent selective cytotoxicity, toward breast cancer cells, including MCF-7 and triple-negative MDA-MB-231, with a favourable selectivity index (>1) compared to MCF-10A cells, and the strongest selectivity observed in the TNBC model at 48 h. In addition, hep-AgNPs showed potent antibacterial activity (IC₅₀ = 24.3 µg/mL) and antifungal activity (IC₅₀ = 6.2 µg/mL for <i>A. fumigatus</i> and 24.43 µg/mL for <i>C. albicans</i>). In addition, they exhibit strong biocompatibility with keratinocytes and fibroblasts.</p><p><strong>Conclusion: </strong>Heparin-capped silver nanoparticles combine the biological functionality of heparin with the antimicrobial and selective cytotoxic properties of the silver nanoparticles. Their selective cytotoxicity, antimicrobial efficacy, and favourable cellular interaction profiles highlight their potential as multifunctional nanoplatforms for applications such as chronic wound management in neutral to alkaline wound environments, and dose-controlled, targeted therapeutic strategies relevant to aggressive cancer models, including TNBC.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"576538"},"PeriodicalIF":6.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837579","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":"Nanomaterial-Mediated Targeting of Mitochondrial Metabolism: Strategies and Applications in Cancer Therapy.","authors":"Yue Hu, Peichen Xie, Jialin Li, Rui Liu, Haotong Wang, Zhicheng Wang, Chunyan Liu","doi":"10.2147/IJN.S603170","DOIUrl":"https://doi.org/10.2147/IJN.S603170","url":null,"abstract":"<p><p>Mitochondria serve as cellular powerhouses and function as central hubs for oxidative metabolism and signaling regulation. These organelles produce ATP primarily through oxidative phosphorylation (OXPHOS), thereby fueling cellular growth and function. In cancer, metabolic reprogramming drives malignant progression, with mitochondria playing a pivotal role. To meet heightened energy and biosynthetic demands, cancer cells modulate mitochondrial OXPHOS activity while enhancing fatty acid oxidation and amino acid metabolism, thereby maintaining redox balance and supporting survival and proliferation. Targeting mitochondrial metabolism with nanomaterials has emerged as a promising strategy for cancer therapy. This review covers advances from 2018-2025, encompassing lipid-based, polymeric, peptide-functionalized, and stimuli-responsive nanocarriers. By employing nanocarriers to deliver metabolic inhibitors or chemotherapeutic agents precisely to mitochondria, this approach can disrupt energy metabolism, impair redox homeostasis, or induce apoptosis in tumor cells. Such targeted intervention not only enhances chemotherapy efficacy but also synergizes with radiotherapy and immunotherapy, offering a potential route to overcome resistance. Despite its considerable promise, several challenges remain in the nanomaterial-based targeting of mitochondrial metabolism, including optimization of targeting efficiency and biosafety. Future efforts should focus on refining these aspects to accelerate the clinical translation of precise mitochondrial metabolism-directed therapies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"603170"},"PeriodicalIF":6.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837560","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":"How Advanced is Nanomedicine to Treat Atherosclerosis? A Comprehensive Review of the Literature.","authors":"Jiahui Zhang, Junran Tong, Yang Sun, Jinpeng Sun, Ran Gao, Di Sun, Xiaopeng Guo, Yumiao Wei","doi":"10.2147/IJN.S563561","DOIUrl":"https://doi.org/10.2147/IJN.S563561","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a major underlying cause of cardiovascular disease. Rupture of unstable atherosclerotic plaques can induce severe acute cardiovascular events and sudden cardiac death. Therefore, developing targeted interventional therapies for atherosclerotic plaques is clinically important to improve cardiovascular mortality. With the advancement of nanomedicine, nanomaterials have demonstrated great potential in atherosclerosis treatment due to their unique compositional/structural features, synthesis strategies, and surface modifications. Based on the pathological characteristics of atherosclerotic plaques, the design and preparation of stimulus-responsive, surface-functionalized, and conditionally-released nanomaterials have become an important approach to achieving precise intervention for atherosclerotic lesions. Considering the pathological features of different cell types involved in AS progression, this review describes the targeting strategies, structural and functional designs, and potential mechanisms of action of targeted nanotherapies in the treatment of atherosclerosis. By summarizing representative recent studies in detail, we reveal the intrinsic interactions and relationships between current targeted nanotherapies and atherosclerotic plaques. Finally, this review provides an outlook on the future application of nanomaterials by presenting key scientific questions that have not yet been addressed, to advance the clinical translation of targeted nanotherapies for atherosclerosis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"563561"},"PeriodicalIF":6.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837597","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":"Microenvironment-Activated Fe-MOF Nanoplatform Enables Controlled Doxorubicin Release and Ferroptosis-Associated Oxidative Damage in MCF-7 Breast Cancer Cells.","authors":"Miao Yuan, Yang Wu, Jing Zheng, Chaoran Wang, Jiarong Wang, Yifan Zheng, Yunqi Wang, Baiqi Wang","doi":"10.2147/IJN.S604452","DOIUrl":"https://doi.org/10.2147/IJN.S604452","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin (DOX) is a cornerstone chemotherapeutic for breast cancer; however, its clinical efficacy is limited by inefficient intracellular delivery and dose-limiting off-target toxicity. Microenvironment-responsive nanoplatforms offer a promising strategy to enhance tumor selectivity and therapeutic performance.</p><p><strong>Methods: </strong>A core-shell nanosystem (UTMD) was constructed by coating an NH₂-MIL-88B(Fe) metal-organic framework (Fe-MOF) shell onto a UCNP@TiO₂ scaffold. The Fe-MOF shell was designed as a dual pH- and glutathione (GSH)-responsive gatekeeper for controlled DOX release. The nanosystem was characterized for structural features, drug loading, and stimulus-responsive release behavior. Cellular uptake, intracellular trafficking, cytotoxicity, and redox-related biochemical changes were evaluated in MCF-7 breast cancer cells and HEK-293 normal cells.</p><p><strong>Results: </strong>UTMD achieved high encapsulation efficiency (86.5%) and maintained stability under physiological conditions, while enabling accelerated DOX release in acidic and reducing environments. The nanosystem enhanced cellular internalization and promoted nuclear accumulation of DOX in MCF-7 cells. In addition, UTMD induced significant intracellular redox imbalance, characterized by GSH depletion, increased reactive oxygen species levels, and elevated lipid peroxidation, accompanied by mitochondrial membrane potential depolarization. These changes are consistent with ferroptosis-associated oxidative damage. Compared with free DOX, UTMD exhibited improved cytocompatibility in HEK-293 cells.</p><p><strong>Discussion: </strong>The Fe-MOF shell functions as a microenvironment-responsive gatekeeper that coordinates controlled drug release with iron-mediated oxidative stress. This integrated design links chemotherapy with ferroptosis-associated mechanisms, improving therapeutic selectivity and mechanistic interpretability.</p><p><strong>Conclusion: </strong>UTMD represents a microenvironment-activated nanoplatform that enables controlled DOX delivery and ferroptosis-associated oxidative damage. This strategy enhances antitumor efficacy while reducing off-target toxicity, offering potential for improved breast cancer therapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"604452"},"PeriodicalIF":6.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837611","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":"From Bench to Bedside: Multifunctional Nanoplatforms in the Fight Against Non-alcoholic Fatty Liver Disease.","authors":"Yu Zhao, Luting Wang, Shengrui Zhu, Rui Feng, Wei Zhang","doi":"10.2147/IJN.S593450","DOIUrl":"https://doi.org/10.2147/IJN.S593450","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population and represents a major public health burden, characterized by disease progression from steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma. Despite this high prevalence and serious clinical outcomes, no pharmacologic therapies are currently approved, and standard lifestyle interventions often prove ineffective. Therefore, there is a major unmet clinical need for innovative treatments. To overcome these limitations, nanomedicine has emerged as a promising approach, with multifunctional nanoplatforms (MFNs) demonstrating distinctive advantages in tackling the complex pathology of NAFLD. For instance, MFNs enable targeted liver delivery, synergistic therapeutic effects (eg, reducing hepatic lipogenesis and fibrosis), and theranostic integration, thereby minimizing rapid clearance and adverse effects associated with conventional low-molecular-weight compounds. Consequently, this review comprehensively synthesizes the latest advances in MFNs for NAFLD management, critically analyzing their design strategies (eg, nanoencapsulation of bioactive compounds for enhanced bioavailability) and mechanistic roles in ameliorating inflammation, fibrosis, and steatosis. Furthermore, it explores challenges such as optimizing organ-specific targeting and personalized applications, while outlining future research directions to accelerate clinical translation and address coexisting conditions like chronic hepatitis B infection. By bridging current knowledge gaps, this work aims to inform the development of effective nanotherapeutic strategies for NAFLD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"593450"},"PeriodicalIF":6.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837549","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":"Advancements in Neonatal Brain Injury Treatment: Nanomedicine-Based Strategies.","authors":"Peili Jin, Chuanchuan He, Xiaojuan Zhang, Yimin Huang","doi":"10.2147/IJN.S597726","DOIUrl":"https://doi.org/10.2147/IJN.S597726","url":null,"abstract":"<p><p>Neonatal brain injury, such as hypoxic-ischemic encephalopathy (HIE), is a leading cause of infant mortality and long-term neurodevelopmental disabilities. Current clinical therapeutic strategies are limited by the blood-brain barrier (BBB), the complexity of the injury cascade, and the narrow therapeutic window. Nanomedicine has shown potential in preclinical studies for overcoming these barriers by leveraging its unique nanoscale characteristics and engineerability design to load, stabilize, and deliver vulnerable biomacromolecules across the compromised BBB to the lesion site. This review presents the first systematic horizontal comparison and critical evaluation of the major nanoplatforms employed in neonatal brain injury therapy. Based on data derived primarily from animal models, we analyze the heterogeneity across studies in model systems, administration routes, and efficacy endpoints, revealing common challenges in the field regarding long-term safety, manufacturability, and reproducibility. This review aims to provide guidance for selecting appropriate nanoplatforms to facilitate the translational advancement of this field toward clinical applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"597726"},"PeriodicalIF":6.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837633","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":"Research Progress on Nanoformulations Based on Active Components from Traditional Chinese Medicine for MASLD.","authors":"Zi-Xiu Gou, Ning-Wei Li, Jun-Yi Yao, Yun-Liang Wang","doi":"10.2147/IJN.S597554","DOIUrl":"https://doi.org/10.2147/IJN.S597554","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease with rising prevalence and disease burden. However, despite recent therapeutic advances, effective and broadly applicable treatment options remain limited, prompting continued efforts to develop novel therapeutic agents. Traditional Chinese Medicine (TCM) has attracted growing interest in MASLD management because its bioactive compounds can target multiple pathogenic processes. However, many TCM-derived compounds are limited by poor solubility, low bioavailability, and insufficient tissue specificity. Nanotechnology-based formulations enable controlled release and targeted delivery, offering a strategy to improve the utilization and therapeutic efficacy of TCM-derived active ingredients against MASLD. Based on a structured literature search across four databases, 45 representative studies were included and narratively synthesized according to nanoplatform type, design features, and mechanism-related therapeutic actions. Compared with previous broader reviews on TCM nanomedicine or MASLD-related nanotherapies, this review particularly emphasizes MASLD-oriented TCM nanoformulations from the perspectives of platform classification, design features, and mechanism-related therapeutic actions. We also discuss current challenges and future directions for clinical translation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"597554"},"PeriodicalIF":6.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837447","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":"How Selective are Nanomaterials to Treat Osteoarthritis.","authors":"Yunpeng Zhang, Xinkun Cheng, Jiwei Tian, Jian Liu, Yuanyin Teng, Junhao Chen, Zhu Wu, Huimin Ding, Zhongsong Zhang","doi":"10.2147/IJN.S601362","DOIUrl":"https://doi.org/10.2147/IJN.S601362","url":null,"abstract":"<p><p>Osteoarthritis (OA) is now increasingly recognized as a disease that affects the entire joint, where synovial inflammation plays a key role in pain, cartilage degeneration, and structural progression. Synovial macrophages (SMs) are key regulators in this process due to their phenotypic plasticity and central roles in amplifying inflammation, disrupting immunometabolism, and interacting with other joint-resident cells. These characteristics make SMs attractive targets for disease-modifying interventions. However, conventional therapies are limited by poor intra-articular retention, low cellular selectivity, and inadequate control over complex pathogenic networks. This review summarizes the biological functions of SMs in OA and explains why they are a mechanistically important and therapeutically accessible target. Next, we provide a structured overview of nanomaterial-based strategies for SM-targeted OA therapy, covering major material platforms, receptor-guided delivery approaches, subset- and state-selective targeting, intracellular functional intervention, and multi-target combination designs. We highlight representative studies that show how nanomedicines can improve local retention, enhance macrophage-specific uptake, and modulate inflammation, metabolism, oxidative stress, and cell fate. Finally, we discuss the major barriers to clinical translation, such as macrophage heterogeneity, safety, pharmacokinetics, and chemistry, manufacturing, and controls (CMC), and outline future directions for biomarker-guided and precision nanotherapy in OA.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"601362"},"PeriodicalIF":6.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837552","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 Advances in Novel Drug Delivery Systems for the Management of Cutaneous Squamous Cell Carcinoma.","authors":"Xiaoyi Fu, Zijian Zhang, Qinyi Dong, Siying Li, Xinman Wang, Han Zhang, Jiahao Bai, Huiyan Han, Lei Shi, Kaili Zheng, Lili Liang","doi":"10.2147/IJN.S592605","DOIUrl":"https://doi.org/10.2147/IJN.S592605","url":null,"abstract":"<p><p>Cutaneous squamous cell carcinoma (cSCC) is a type of cancer that originates from the growth of skin cells. It represents the second most common form of non-melanoma skin cancer and primarily arises from the malignant proliferation of keratinocytes in the epidermis or skin appendages. The global incidence of cSCC is increasing, and its onset is primarily associated with prolonged exposure to ultraviolet radiation, genetic susceptibility, and immunosuppression. These factors severely impair patients' quality of life and skin health. Conventional therapeutic strategies for cSCC mainly rely on surgery, radiotherapy, or photodynamic therapy. Although these approaches are widely applied in clinical practice, they present several limitations, including high recurrence rates, poor suitability for special populations, and significant toxic side effects. To overcome these shortcomings, researchers worldwide have recently conducted extensive studies on novel therapeutic approaches. Among them, innovative drug delivery systems have emerged as a highly promising research direction. Unlike traditional treatments, these new drug delivery systems, including nanocarriers (liposomes, polymeric nanoparticles, inorganic nanoparticles), microneedle arrays, hyaluronic acid-based carriers, and DNA nanocomposites, can precisely deliver therapeutic agents to cSCC lesions, reduce systemic toxicity, and achieve sustained drug release at the tumor site. These advantages make them an optimal option for cSCC therapy. This study provides a comprehensive summary of recent advances in the design, functional performance, and translational prospects of these novel delivery technologies. It particularly elucidates how they overcome the limitations of conventional therapies and offer new possibilities for developing effective treatment strategies for cSCC.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"592605"},"PeriodicalIF":6.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837648","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}