International Journal of Nanomedicine最新文献

{"title":"Optimized Nanostructured Lipid Carriers for Metformin: Enhanced Anti-Inflammatory Activity and Protection Against Type 2 Diabetes-Induced Organ Damage.","authors":"Mona Qushawy, Mansuor A Alanazi, Wafaa M Hikal, Palanisamy Amirthalingam, Eman Abu-Gharbieh, Wejdan Saleh Almanzalawi, Yasmin Mortagi, Nehal Elsherbiny, Amira M Elsherbini","doi":"10.2147/IJN.S506631","DOIUrl":"10.2147/IJN.S506631","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is a chronic metabolic disease that causes serious consequences in different organs such as the heart, kidneys, pancreas, and liver. Metformin (MTF) is a common treatment for type 2 diabetes. It controls the blood glucose level by improving insulin sensitivity and glucose absorption. MTF belongs to BCS class III, which is characterized by high solubility and low permeability. Several types of nanoparticles have been developed to overcome the permeability problem of MTF.</p><p><strong>Methods: </strong>In this study, we prepared nanostructured lipid carriers (NLCs) loaded with metformin (MTF) using hot melt homogenization-ultrasonication. To select the best formulation, the prepared MTF-NLCs were evaluated for entrapment efficiency % (EE%), particle size, zeta potential, polydispersity index (PDI), and in vitro drug release. The optimized formulation was selected based on the high EE%, small particle size, high absolute zeta potential, low polydispersity index, and high in vitro drug release. The optimized formulation was evaluated for surface morphology by transmission electron microscope (TEM) and for further biochemical and histological analyses in a high-fat diet-induced type 2 diabetes mellitus (T2DM) in vivo rat model; HFD was administered (44.3-kJ/kg total energy) for four weeks, followed by a single intraperitoneal injection of streptozotocin (STZ). Rats were allocated into four groups; Diabetic (DM), DM+MTF, DM+MTF-NLC, and control group. Serum and tissue samples were processed for inflammatory markers detection and histopathology.</p><p><strong>Results: </strong>The prepared MTF-NLC formulation exhibited high EE% (80.65 ± 1.95% to 99.31 ± 3.25%), small particle size (247.72±5.74nm-503.23±7.26nm), high negative zeta potential (from -31.83‎±‎0.98mV to -51.6‎±‎2.64mV), PDI value less than 0.5 for all MTF-NLCs, and controlled drug release. MTF-NLC7 appeared spherical when examined by TEM. MTF and MTF-NLC groups significantly alleviated the degenerative effects of DM in both submandibular glands (SMG) and pancreas. Additionally, treatments improved kidney and liver function reduced serum inflammatory cytokines, and tissue SMG and pancreatic immunostaining of inflammatory cytokines with favorable effects of MTF-NLCs. Moreover, the MTF-NLCs showed a significant reduction of serum inflammatory cytokines, including (TNF-α and IL-1β) and pancreatic TNF-α expression, in addition to ameliorating liver and renal functions compared to MTF alone.</p><p><strong>Conclusion: </strong>The preparation of MTF as NLCs improved its permeability, enhancing its anti-inflammatory activity and providing more protection against diabetes-induced organ injury.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3765-3788"},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752541","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":"Targeting Delivery of Dexamethasone to Inflamed Joints by Albumin-Binding Peptide Modified Liposomes for Rheumatoid Arthritis Therapy.","authors":"Huan Wang, Rui Gou, Wei Li, Zhoujiang Chen, Chun Gu, Sanjun Shi, Liang Zou, Hanmei Li","doi":"10.2147/IJN.S486488","DOIUrl":"10.2147/IJN.S486488","url":null,"abstract":"<p><strong>Introduction: </strong>Delivering the anti-inflammatory dexamethasone in nanoformulations is important for reducing off-target effects when treating rheumatoid arthritis. Nanoformulations can be targeted to sites of inflammation by modifying the nanoparticles with albumin before administration, but such particles can be unstable in vivo.</p><p><strong>Methods: </strong>Here, we have developed and validated an alternative targeting in which dexamethasone-loaded liposomes were modified with a 46-residue peptide called \"albumin-binding domain\", such that the liposomes would adsorb endogenous albumin after administration.</p><p><strong>Results: </strong>The resulting liposomes were small (90 nm diameter) and uniformly dispersed, and both X-ray diffraction and differential scanning calorimetry confirmed efficient dexamethasone encapsulation. Functionalizing the liposomes with albumin-binding peptide strongly increased not only their binding to albumin in vitro but also their uptake by RAW264.7 cells in culture. After injection into rats with adjuvant-induced arthritis, the liposomes accumulated and persisted at sites of inflammation, effectively inhibiting joint swelling and reducing the level of the inflammatory factors TNF-α and IL-1β in joints. The liposomes decorated with the albumin-binding peptide did not display obvious hepatotoxicity and did not reduce red and white blood cells number.</p><p><strong>Discussion: </strong>Our results validate modifying liposomes with albumin-binding domain as a way to target them to sites of inflammation for efficient drug delivery against rheumatoid arthritis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3789-3802"},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752542","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":"Enhanced Long-Term Antibacterial and Osteogenic Properties of Silver-Loaded Titanium Dioxide Nanotube Arrays for Implant Applications.","authors":"Yicun Yao, Peifen Lin, Dongping Ye, Haixiong Miao, Lin Cao, Peng Zhang, Jiake Xu, Libing Dai","doi":"10.2147/IJN.S493754","DOIUrl":"10.2147/IJN.S493754","url":null,"abstract":"<p><strong>Objective: </strong>This study explored constructing silver-loaded titanium dioxide nanotube (TiO₂ NT) arrays on titanium surfaces using anodic oxidation combined with ion implantation. We assessed the cytocompatibility, antibacterial properties, and osteogenic potential of these silver-loaded TiO₂ NT arrays, along with the underlying mechanisms.</p><p><strong>Methods: </strong>We utilized anodization to create TiO₂ NT arrays and employed ion implantation to load silver ions, categorizing samples into groups NT-Ag-II-L, NT-Ag-II-M, and NT-Ag-II-H based on different Ag ion dosages. Characterization was performed via scanning electron microscopy (SEM). We evaluated cell compatibility and assessed the antimicrobial performance and Ag ion release profiles. The osteogenic ability of the samples was measured, and the effects on ERK5 and osteogenesis-related factors were analyzed. To clarify the role of ERK5 in osteogenesis, we inhibited the ERK5 pathway using BIX02188 and subsequently re-evaluated osteogenic capacity in co-cultured cells.</p><p><strong>Results: </strong>SEM analysis showed that in the NT-Ag-II-M group, Ag ions exhibited a flake-like distribution atop the TiO₂ NTs, while NT-Ag-II-L and NT-Ag-II-H groups presented clustered grid structures. Energy-filtered transmission electron microscopy (EFTEM) confirmed orderly Ag ion arrangements within the lumens of the nanotubes. Notably, the silver-loaded TiO₂ NT arrays did not inhibit MC3T3-E1 cell proliferation and enhanced early cellular adhesion. All samples displayed significant antimicrobial activity initially, which decreased after seven days; however, Ag ion release decreased gradually over the first 14 days before stabilizing. Additionally, the samples increased alkaline phosphatase activity, collagen secretion, and extracellular matrix mineralization, up-regulating ERK5 and other osteogenic factors. Inhibition of the ERK5 pathway suppressed the osteogenic capabilities of the samples.</p><p><strong>Conclusion: </strong>Anodization and ion implantation successfully produced silver-loaded TiO₂ NT arrays on titanium surfaces, demonstrating no cytotoxicity, sustained antimicrobial properties, and enhanced osteogenic potential. The antimicrobial effect relates to silver ion release, whereas osteogenesis is promoted by ERK5 signaling triggered by silver ions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3749-3764"},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752538","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":"Emo@KP MBs Modulates the TGF-β1/Smad Signaling Pathway by in situ Micro-Nano Conversion to Reduce Renal Inflammation and Fibrosis Caused by Unilateral Ureteral Obstruction.","authors":"Jinxia Zhang, Xinxin Xie, Yuanjing Li, Haonan Wang, Lijuan Zhang, Peiqi Shi, Jing Wei, Ling Zhang, Yingdong Lu, Ligang Cui, Xiaoning Liu, Xiaolong Liang","doi":"10.2147/IJN.S499550","DOIUrl":"10.2147/IJN.S499550","url":null,"abstract":"<p><strong>Introduction: </strong>Emodin alleviates renal interstitial fibrosis (RIF) and reduces inflammation by inhibiting the TGF-β1/Smad pathway, thus improving CKD outcomes. However, its clinical use is limited due to poor solubility and side effects. This study developed a targeted drug delivery system using αKIM-1 modified microbubbles carrying Emodin to enhance accumulation in renal tissues with high KIM-1 expression.</p><p><strong>Methods: </strong>Emo@KP MBs were characterized by TEM and DLS, and their drug loading and encapsulation rates were measured by UV-VIS-NIR spectroscopy. Biocompatibility was assessed in vitro with HK-2 cells and in vivo via hematological and pathological markers. Contrast-enhanced ultrasound (CEUS) and fluorescence imaging were used for real-time visualization of treatment. Therapeutic experiments were performed on a unilateral ureteral obstruction (UUO) mouse model treated with Emo@KP MBs + US on days 1 and 3 post-surgery. Renal function, cytokine levels, and histological analysis were detected to evaluate therapeutic effects.</p><p><strong>Results: </strong>Emo@KP MBs exhibited spherical structures (2 ~ 4 μm) with good stability. Ultrasound targeted microbubble destruction (UTMD) enabled controlled release of Emodin. CEUS and fluorescence imaging showed enhanced drug accumulation in diseased kidneys. In the UUO + Emo@KP MBs/US group, renal function was improved, inflammatory cytokines (IL-1β, TNF-α) were decreased, and renal lesions and collagen deposition were reduced. Immunohistochemistry revealed the downregulation of TGF-β, Smad2/3, and α-SMA, and upregulation of E-cadherin.</p><p><strong>Conclusion: </strong>Emo@KP MBs enhanced drug delivery efficiency and therapeutic efficacy through αKIM-1 targeting and UTMD, while providing real-time imaging capabilities, suggesting good potential as a therapeutic approach to reduce renal inflammation and fibrosis in UUO.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3731-3747"},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752537","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":"Core-Shell Magnetic Nanocarriers: Fe₃O₄-Hydroxyapatite/Polysuccinimide Hybrids for Enhanced Oral Bioavailability of Fluorouracil.","authors":"Wenhui Zhang, Qiang Wang, Fengguo Zhai, Xingjun Fan, Fanqin Meng, Guangzhi Shen, Ying Zhu, Jingdan Cao, Fengbo Yu","doi":"10.2147/IJN.S507458","DOIUrl":"10.2147/IJN.S507458","url":null,"abstract":"<p><strong>Objective: </strong>This study pioneers a pH-responsive core-shell nanoplatform integrating magnetic Fe₃O₄-hydroxyapatite (Fe/HAP) with polysuccinimide (PSI) polymer, engineered to enhance tumor-targeted delivery of fluorouracil (5-FU) for liver cancer therapy.</p><p><strong>Methods: </strong>The individual components-hydroxyapatite (HAP), magnetite (F₃O₄), iron-doped hydroxyapatite (Fe/HAP), and polysuccinimide (PSI)-were synthesized and systematically characterized through Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Through a combination of single-factor experiments and Box-Behnken design (BBD) response surface methodology, the formulation parameters were optimized for two nanoparticle systems: (1) non-magnetic 5-FU-loaded PSI-HAP (designated as 5-FU@DC, where DC denotes \"drug carrier\") and (2) magnetic-targeted formulations 5-FU@PSI-Fe/HAP with varying iron content (5-FU@FeDC20, 5-FU@FeDC30, 5-FU@FeDC40). The engineered nanoparticles were thoroughly characterized for their morphological characteristics, hydrodynamic properties (particle size distribution and zeta potential), magnetic responsiveness (vibrating sample magnetometry), and pH-dependent drug release profiles. Nile Red was used to label the drug-loaded nanoparticles, and small animal imaging technology was employed to track their distribution in mice in vivo. Furthermore, in vitro studies examined the effects of these formulations on the proliferation, apoptosis, and migration of Huh-7 liver cancer cells.</p><p><strong>Results: </strong>The formulations (5-FU@DC and 5-FU@FeDC) were found to form uniform spherical or near-spherical nanoparticles. Vibrating sample magnetometer (VSM) analysis confirmed that the 5-FU@FeDC formulations displayed paramagnetic properties. Zeta potential measurements showed that all prepared systems had negative charges, similar to human biological membranes. All nanoparticles gradually released the drug at pH levels above 5, with the release rate increasing as the pH increased. Compared to the non-magnetic 5-FU@DC formulation, the magnetic 5-FU@FeDC formulations showed significantly longer distribution and retention times in liver tissue and more effectively inhibited the proliferation of Huh-7 cells.</p><p><strong>Conclusion: </strong>The current study developed a magnetic targeting nano-delivery system using PSI and Fe/HAP as formulation excipients. The system offers uniform particle size, a simple preparation process, and a cost-effective method for targeted drug delivery. It is not only suitable for liver-targeted drug delivery but also applicable for drug delivery to other tissues in the body for anti-tumor drugs.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3671-3695"},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700318","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":"Early Detection of Brain Metastases from Triple-Negative Breast Cancer with a Tumor-Targeting Dual-Modal MR/NIRF Imaging Probe.","authors":"Fang Nie, Lin Li, Yingying Bai, Jian Yang","doi":"10.2147/IJN.S498629","DOIUrl":"10.2147/IJN.S498629","url":null,"abstract":"<p><strong>Objective: </strong>Imaging early-stage brain metastases from triple-negative breast cancer (TNBC) is challenging due to the blood-brain barrier (BBB). To address this issue, we developed Den-Angio-GE11, a nanoprobe engineered to traverse the BBB and selectively target metastatic cells.</p><p><strong>Methods: </strong>A TNBC brain metastasis model was established in mice through intracardiac injection of MDA-MB-231 brain-seeking cells (MDA-MB-231-BR). Metastatic lesions were longitudinally monitored using T2-weighted magnetic resonance imaging (MRI) and confirmed through contrast-enhanced MRI with Gadolinium-DTPA (Gd-DTPA). The Den-Angio-GE11 nanoprobe was synthesized on a polyamidoamine (PAMAM)-G5 dendrimer platform, incorporating Angiopep-2 and GE11 peptides for BBB traversal and metastatic cell targeting. Dual-modal imaging capability was achieved by conjugating Gd-DTPA for MRI and NIR783 for near-infrared fluorescence (NIRF) imaging.</p><p><strong>Results: </strong>Den-Angio-GE11 demonstrated significantly enhanced affinity to EGFR compared to controls, as confirmed by immunofluorescence staining and flow cytometry assays. Brain metastases appeared on T2-weighted MRI three weeks post-injection of MDA-MB-231BR cells and maintained uncompromised BBB function for another one or two weeks, as demonstrated by a lack of enhancement in Gd-DTPA-enhanced MRI. Compared to control nanoparticles, Den-Angio-GE11 remarkably enhanced T1 and NIRF signals of lesions after administration. Histological analysis confirmed Den-Angio-GE11 targeting brain metastatic cells. For lesions in extreme-early stage (undetectable by T2-weighted imaging), NIRF imaging post-Den-Angio-GE11 administration successfully indicated potential lesions. Fluorescence imaging analyses further verified Den-Angio-GE11 targeted sporadically metastatic cells in the brain parenchyma.</p><p><strong>Conclusion: </strong>Early brain metastases of TNBC can be detected by Den-Angio-GE11 through T1-weighted MRI or NIRF imaging.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3697-3712"},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709662","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":"Cutaneous Evaluation of Fe₃O₄ Nanoparticles: An Assessment Based on 2D and 3D Human Epidermis Models Under Standard and UV Conditions.","authors":"Claudia Geanina Watz, Elena-Alina Moacă, Andreea Cioca, Lenuța Maria Șuta, Lavinia Krauss Maldea, Ioana Zinuca Magyari-Pavel, Mirela Nicolov, Ioan-Ovidiu Sîrbu, Felicia Loghin, Cristina A Dehelean","doi":"10.2147/IJN.S513423","DOIUrl":"10.2147/IJN.S513423","url":null,"abstract":"<p><strong>Purpose: </strong>The high-speed development of nanotechnology industry has fueled a plethora of engineered nanoparticles (NPs) and NP-based consumer products, further leading to massive and uncontrolled human exposure. In this regard, the researches addressing the safety assessment of NPs should be re-approached from the perspective of test parameters variety, closely simulating daily life scenarios. Therefore, the present study adopts complex in vitro models to establish the safety profile of Fe₃O₄ NPs, by using 2D and 3D human epidermis models under both standard and UV exposure conditions.</p><p><strong>Methods: </strong>Advanced 3D human reconstructed epidermal tissues and two different monolayers of immortalized human cells (keratinocytes and fibroblasts), using series of in vitro assays were employed in the current study to evaluate multiple biological responses, as follows: i) divers protocols (skin irritation, phototoxicity assay); ii) different conditions (± UV exposure) and iii) a wide variety of quantification methods, such as: MTT, NR and LDH colorimetric tests - performed to evaluate the viability of the cells/microtissues, respectively, the cytotoxicity of the test compounds. In addition, IL-1α ELISA assay was used to quantify the inflammatory activity induced by the test samples, while immunocytochemistry analysis through fluorescent microscopy was employed to provide insightful information regarding the possible mechanism of action of test samples.</p><p><strong>Results: </strong>The two test samples (S₁ and S₂) induced a higher cell viability decrease on immortalized human keratinocytes (HaCaT) compared to human fibroblasts (1BR3), while 3D-epidermis microtissues showed similar viabilities when treated with both samples under standard conditions (-UV rays) - for both type of evaluation protocols: skin irritation and phototoxicity. However, UV irradiation of 3D-microtissues pre-exposed to test samples led to different results between the two test samples, revealing that S₂ sample induced a significant impairment of human epidermis viability, whereas S₁ sample elicited an activity similar to the one recorded under standard conditions (-UV).</p><p><strong>Conclusion: </strong>The present results indicate significant differences in toxicity between the two in vitro models under UV conditions, highlighting the importance of model selection and exposure parameters in assessing NP safety. Thus, our findings suggest that Fe₃O₄ NPs may pose some risks under specific environmental conditions, within the limitations of the experimental setup, and further research is needed to refine safety guidelines.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3653-3670"},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700337","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":"Hypericin Nanoparticles-Associated Photodynamic Therapy Modulates the Biological Behavior of Hepatocellular Carcinoma by SERPINE1.","authors":"Xuanzhi Yan, Jiaxing Fan, Wanying Qin, Minjun Liao, Siming Li, Liya Suo, Yujin Xie, Xin Jiang, Dengfeng Zou, Weijia Liao","doi":"10.2147/IJN.S507037","DOIUrl":"10.2147/IJN.S507037","url":null,"abstract":"<p><strong>Background: </strong>In recent years, photodynamic therapy (PDT) has gradually attracted the attention of researchers due to its therapeutic potential for treating malignant tumors. Hypericin (HC) is anticipated to enhance the therapeutic effect on tumors as an efficient photosensitizer (PS) for PDT. However, the role and mechanism of PDT in hepatocellular carcinoma (HCC) remain unclear.</p><p><strong>Methods: </strong>In this study, we investigated the efficacy of hypericin nanoparticles (HC-NPs)-associated PDT (HC-NPs-PDT) on HCC to explore its anti-HCC mechanism both in vitro and in vivo. Cellular molecular experiments, as well as HCC mouse tumor models, were utilized to validate the impact of HC-NPs-PDT on HCC. Additionally, molecular docking and related experiments were employed to investigate its potential mechanism.</p><p><strong>Results: </strong>Our findings demonstrated that HC-NPs-PDT effectively inhibits the viability, migration, and invasion abilities of HCC cells, as well as suppresses the growth of subcutaneous HCC tumors in BALB/C-nu nude mice. SERPINE1 (also known as PAI, PAI-1, PAI1, PLANH1) may be a key target of HC, as its mRNA and protein levels were significantly up-regulated following HC-NPs-PDT. This upregulation led to a decrease in mitochondrial membrane potential and promoted apoptosis of HCC cells. Additionally, inhibition of SERPINE1 partially restored changes in mitochondrial membrane potential.</p><p><strong>Conclusion: </strong>These results suggest that HC-NPs-PDT may regulate the biological behavior of HCC by upregulating SERPINE1 expression, offering a new perspective for treating HCC.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3713-3730"},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700340","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":"Enhanced Antitumor Immunity Through T Cell Activation with Optimized Tandem Double-OX40L mRNAs.","authors":"Zhuoya Deng, Yuying Tian, Jing Wang, Yongru Xu, Zherui Liu, Zhaohui Xiao, Zhaohai Wang, Minggen Hu, Rong Liu, Penghui Yang","doi":"10.2147/IJN.S479434","DOIUrl":"10.2147/IJN.S479434","url":null,"abstract":"<p><strong>Purpose: </strong>The tumor immune microenvironment (TIME) is often dysfunctional and complex, contributing to tumor metastasis and drug resistance. This study investigates the use of mRNA-based cancer agents as promising tools to combat and reverse refractory TIME conditions.</p><p><strong>Methods: </strong>We optimized and engineered an mRNA cancer agent encoding double tandemly repeated sequences of the T cell costimulator Oxford 40 ligand (diOX40L). The diOX40L mRNAs were encapsulated into lipid nanoparticles (LNPs) for effective delivery. The research explored its safety and antitumor effects through a series of in vivo and in vivo experiments.</p><p><strong>Results: </strong>Our results demonstrate that diOX40L mRNAs efficiently express increased levels of OX40L proteins. The optimized diOX40L mRNA cancer agent generated potent immune costimulatory signals within the TIME, leading to decreased tumor growth and improved survival compared to the original sequence agent. OX40L expression in subcutaneous tumors promoted CD4⁺ and CD8⁺ T cell activation, resulting in heightened IFN-γ and IL-2 secretion and robust immune responses. Combination therapy involving PD-1 antibodies and diOX40L substantially enhanced antitumor efficacy, with increased infiltration of activated CD4⁺ and CD8⁺ T cells.</p><p><strong>Discussion: </strong>In conclusion, our findings highlight the therapeutic potential of the optimized diOX40L mRNA cancer agent in cancer treatment and its potential as an innovative alternative to protein-based therapies. The study underscores the significance of mRNA-based agents in modulating the immune microenvironment and enhancing antitumor responses.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3607-3621"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692160","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":"Tumor Microenvironment Responsive and Platelet Membrane Coated Polydopamine Nanoparticles for Cancer Radiosensitization by Inducing Cuproptosis.","authors":"Le Xin, Shipeng Ning, Hongwei Wang, Runze Shi","doi":"10.2147/IJN.S504148","DOIUrl":"10.2147/IJN.S504148","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis, distinguished from apoptosis, necroptosis, pyroptosis, and ferroptosis, is a current form of programmed cell death that provides novel strategies for tumor therapy. Nanotechnology inducing cuproptosis showed potential in tumor ablation. However, these strategies might induce cellular damage due to a lack of tumor-targeting ability or insufficient tumor inhibition alone.</p><p><strong>Methods: </strong>Here, biomimetic copper-doped polydopamine nanoparticles (PC NPs) were developed to specifically induce tumor cell cuproptosis to enhance radiotherapy (RT). PC NPs were characterized before application for tumor ablation.</p><p><strong>Results: </strong>These PC NPs improve tumor targeting and accumulation. After entering the tumor region, PC degrades in cells responsive to acidic tumor microenvironment (TME). Next, Cu²⁺ is reduced to Cu⁺ after consuming overexpressed glutathione (GSH), which induces dihydrolipoamide S-acetyltransferase (DLAT) aggression and cuproptosis. Under RT, reactive oxygen species (ROS) are generated and consume GSH, leading to cuproptosis. The decreasing of GSH content in tumor tissues can improve the treatment effect of RT by inhibiting self-repair of tumor cells, hindering cell survival and proliferation. The combination of PC and RT alleviate tumor growth, reaching a tumor growth inhibition rate of 93.0%.</p><p><strong>Conclusion: </strong>This tumor-specific targeting nano platform is a valuable radiosensitizer responsive to TME for improving therapeutic efficacy against tumors.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3643-3652"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691942","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}