International Journal of Nanomedicine最新文献

{"title":"A Novel Systemic siDR6 Delivery System Based on DP7-C for the Treatment of Metastatic Lung Cancer.","authors":"Hongyou Zhou, Rui Zhang, Ke Men, Lin Tang, Yusi Wang, Li Yang","doi":"10.2147/IJN.S488213","DOIUrl":"10.2147/IJN.S488213","url":null,"abstract":"<p><strong>Background: </strong>The treatment of metastatic lung cancer, a common complication of many primary cancers, has historically been a significant clinical challenge. Once lung metastasis occurs, patients' survival is often significantly shortened. Therefore, prevention and treatment of lung metastases is an important aspect of cancer treatment. In this study, a simple, low-toxicity, cholesterol-modified cationic cell-penetrating peptide DP7 (DP7-C), in combination with siDR6 was used for intravenous administration for the treatment of lung metastases.</p><p><strong>Methods: </strong>Initially, clinical databases were analyzed to determine the expression levels of death receptor 6 (DR6) in metastatic tumors and the correlation between DR6 expression and patient survival times. The DP7-C/siDR6 micelles were prepared by a self-assembly method. By cultivating 293T, B16F10 and LL2 cells, the in vitro experiments were performed to assess the transfection efficiency, safety and anti-cancer ability of DP7-C/siDR6, while its targeting efficiency and prevention of lungs were investigated by mouse experiments. Furthermore, the therapeutic efficacy of DP7-C/siDR6 was demonstrated in the LL2 model of lung cancer in situ, the B16F10 model of artificial lung metastasis, and the 4T1 model of spontaneous lung metastasis.</p><p><strong>Results: </strong>The clinical data analysis revealed that DR6 was highly expressed in the majority of metastatic tumors and that patients with high DR6 expression exhibited significantly shorter survival times. The DP7-C/siDR6 showed high transfection efficiency, and it could inhibit tumor cell growth by suppressing the STAT3 signaling pathway. Subsequent mouse experiments demonstrated that intravenous administration of DP7-C/siDR6 resulted in efficient lung targeting. The inhibition of DR6 expression on lung endothelial cells was found to prevent metastasis-induced primary necrosis of lung endothelial cells, thereby preventing tumor metastasis. And the DP7-C/siDR6 treatment showed excellent therapeutic efficacy in the tumor models.</p><p><strong>Conclusion: </strong>The systemic delivery of DP7-C micelles carrying siDR6 provide an alternative therapeutic strategy to halt cancer lung metastasis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3623-3642"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692093","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":"Wolf in Sheep's Clothing: Taming Cancer's Resistance with Human Serum Albumin?","authors":"Iga Stukan, Anna Żuk, Kamila Pukacka, Julia Mierzejewska, Jakub Pawłowski, Bogusław Kowalski, Maria Dąbkowska","doi":"10.2147/IJN.S500997","DOIUrl":"10.2147/IJN.S500997","url":null,"abstract":"<p><p>Human serum albumin (HSA) has emerged as a promising carrier for nanodrug delivery, offering unique structural properties that can be engineered to overcome key challenges in cancer treatment, especially resistance to chemotherapy. This review focuses on the cellular uptake of albumin-based nanoparticles and the modifications that enhance their ability to bypass resistance mechanisms, particularly multidrug resistance type 1 (MDR1), by improving targeting to cancer cells. In our unique approach, we integrate the chemical properties of albumin, its interactions with cancer cells, and surface modifications of albumin-based delivery systems that enable to bypass resistance mechanisms, particularly those related to MDR1, and precisely target receptors on cancer cells to improve treatment efficacy. We discuss that while well-established albumin receptors such as gp60 and gp18/30 are crucial for cellular uptake and transcytosis, their biology remains underexplored, limiting their translational potential. Additionally, we explore the potential of emerging targets, such as cluster of differentiation 44 (CD44), cluster of differentiation (CD36) and transferrin receptor TfR1, as well as the advantages of using dimeric forms of albumin (dHSA) to further enhance delivery to resistant cancer cells. Drawing from clinical examples, including the success of albumin-bound paclitaxel (Abraxane) and new formulations like Pazenir and Fyarro (for Sirolimus), we identify gaps in current knowledge and propose strategies to optimize albumin-based systems. In conclusion, albumin-based nanoparticles, when tailored with appropriate modifications, have the potential to bypass multidrug resistance and improve the targeting of cancer cells. By enhancing albumin's ability to efficiently deliver therapeutic agents, these carriers represent a promising approach to addressing one of oncology's most persistent challenges, with substantial potential to improve cancer treatment outcomes.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3493-3525"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691944","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":"Targeted Nanoclusters for Intratracheal Delivery in Intraoperative Imaging of Lung Adenocarcinoma.","authors":"Lu Tang, Ning Li, Zhe Yang, Yangliu Lin, Ge Gao, Quan Lin, Yue Wang","doi":"10.2147/IJN.S509009","DOIUrl":"10.2147/IJN.S509009","url":null,"abstract":"<p><strong>Background: </strong>Computed tomography (CT) is widely used all over the world, and the detection rate of early lung adenocarcinoma is increasing. Minimally invasive thoracic surgery (MITS) has emerged as the preferred surgical approach for lung adenocarcinoma, but identifying small lung adenocarcinomas is difficult. Therefore, there is a need for a non-invasive, convenient and efficient way to localize lung adenocarcinomas.</p><p><strong>Materials and methods: </strong>A targeted gold nanocluster for intraoperative fluorescence imaging by intratracheal delivery has been designed. Au-GSH-anti Napsin A nanoclusters (NapA-AuNCs) were synthesized, and their physicochemical properties and optical properties were characterized. Target effect, cytotoxicity and fluorescence time curve of NapA-AuNCs, were tested in vivo and in vitro, and intratracheal delivery was also carried.</p><p><strong>Results: </strong>NapA-AuNCs targeting lung adenocarcinoma with red fluorescence and good mucus penetration were synthesized, which had the targeting property of A549 and lung adenocarcinoma tissue, and also had very low toxicity to normal lung epithelial cells and organs. Intracheal delivery involves faster imaging of lung adenocarcinoma and less accumulation of other organs than intravenous administration.</p><p><strong>Conclusion: </strong>NapA-AuNCs targeting lung adenocarcinoma were successfully conjugated, and intratracheal delivery is a safe, effective for lung adenocarcinoma intraoperative localization.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3575-3594"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691997","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":"Sericin-Assisted Green Synthesis of Gold Nanoparticles as Broad-Spectrum Antimicrobial and Biofilm-Disrupting Agents for Therapy of Bacterial Infection.","authors":"Rui Cai, Qian Cheng, Jiayu Zhao, Peirong Zhou, Zhaodan Wu, Xuemin Ma, Yajuan Hu, Huiyue Wang, Xiaorong Lan, Jing Zhou, Gang Tao","doi":"10.2147/IJN.S494616","DOIUrl":"10.2147/IJN.S494616","url":null,"abstract":"<p><strong>Background: </strong>Tens of millions of people die from wound infections globally each year, and nearly 80% of tissue infections are associated with bacterial biofilms. However, overuse of antibiotics can lead to bacterial resistance. Therefore, it is critical to develop simple and effective strategies to kill bacteria and remove biofilms.</p><p><strong>Methods: </strong>The present study used sericin as a reducing and stabilizing agent to synthesize sericin-gold nanoparticles (Ser-Au NPs) and tested its colloidal stability under different pH and salt concentration conditions. Subsequently, functional gold nanocomposites (Ser-Au@MMI) were synthesized by combining Ser-Au NPs with 2-mercapto-1-methylimidazole (MMI). The antimicrobial effect of Ser-Au@MMI was checked by MIC, antimicrobial activity test, and in vitro cytotoxicity was assessed using CCK-8 assay. In vitro anti-biofilm effect was observed by fluorescence microscopy and SEM. Finally, the anti-infective therapeutic efficacy of Ser-Au@MMI was determined in an in vivo rat-infected wound model.</p><p><strong>Results: </strong>Sericin as a reducing and stabilizing agent to synthesize Ser-Au NPs exhibited excellent colloidal stability under different pH and salt concentration conditions. The TEM, EDS, and XPS analyses confirmed the successful synthesis of Ser-Au@MMI. It exhibited higher antibacterial activity due to the synergistic effect of MMI and AuNP, which can achieve a bactericidal effect by destroying the integrity of bacterial cell walls and structure. In addition, Ser-Au@MMI₁₀ (HAuCl₄:MMI =1:10) concentration (64 μg/mL) could effectively disrupt biofilms formed by four species of bacteria and kill them, including <i>P. aeruginosa, B. subtilis, E. coli</i>, and <i>S. aureus</i>, but was not cytotoxic to mouse fibroblasts (L929) cells. Infected wound modeling showed that Ser-Au@MMI₁₀ accelerated infected wound healing in vivo.</p><p><strong>Conclusion: </strong>Ser-Au@MMI nanocomposites are prepared through a facile and environmentally friendly strategy and have the advantages of excellent bactericidal effect and low toxicity, which has the potential for application as a broad-spectrum antimicrobial agent and biofilm disrupting agent in healthcare.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3559-3574"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691965","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":"SYL3C Aptamer-DNA Tetrahedra Conjugates Enable Near-Infrared Fluorescent Imaging of Colorectal Cancer.","authors":"Zhidie Huang, Pinghui Li, Yiwen Li, Xiaoyan Duan, Mengting Li, Dawei Jiang, Jianbo Li","doi":"10.2147/IJN.S510964","DOIUrl":"10.2147/IJN.S510964","url":null,"abstract":"<p><strong>Purpose: </strong>SYL3C is an optimized DNA aptamer with high selectivity and affinity for the epithelial cell adhesion molecule (EpCAM), an overexpressed tumor antigen in colorectal cancer (CRC). While its cellular affinity has been validated, in vivo studies are lacking.</p><p><strong>Methods: </strong>This study modifies SYL3C with the fluorescent motif Cy7 to evaluate its metabolism and diagnostic potential in EpCAM-positive HT-29 xenograft mice using near-infrared fluorescence (NIRF). We also employ DNA Tetrahedra (DTN) to load the Cy7-DTN-SYL3C probe and assess whether this strategy improves circulation and tumor uptake of SYL3C.</p><p><strong>Results: </strong>Cy7-SYL3C is primarily metabolized by the kidneys and enables targeted imaging of HT-29 tumors, outperforming untargeted Cy7-DTN. The DTN coupling strategy prolongs SYL3C metabolism and enhances tumor probe uptake about twice higher than Cy7-SYL3C over 24 hours.</p><p><strong>Conclusion: </strong>This study presents preliminary evidence for the SYL3C aptamer's potential in vivo imaging of EpCAM-positive CRC. The DTN conjugation strategy may extend the aptamer's metabolic stability and improve tumor uptake, expanding its applications in CRC diagnosis and treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3595-3606"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691982","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":"The Potential of Nano-Formulated Natural Drugs in Melanoma Treatment: A Review of Pharmacological Efficacy and Mechanistic Insights.","authors":"Bowen Wang, Yinan Wang","doi":"10.2147/IJN.S505394","DOIUrl":"10.2147/IJN.S505394","url":null,"abstract":"<p><p>Melanoma is a very aggressive skin cancer; its treatment bears great challenges, hence the interest in new therapeutic approaches is growing. In this review, potential nano-formulated natural drugs from plants such as Ginseng, Pistacia lentiscus, Amaranthus hypochondriacus, and Cannabis sativa in the treatment of melanoma are discussed. We discuss various characteristics of nanoformulations, including liposomes and nanoemulsions, with respect to their ability in enhancing drug delivery and bioavailability. Key mechanisms of action including reactive oxygen species modulation, apoptotic signaling induction, immune modulation through TLR4/MyD88, and inhibition of angiogenesis by VEGF pathways are discussed. Although these natural nanoformulations show promise in improving therapeutic outcomes, challenges related to their clinical application and safety persist. Further research is warranted to fully explore how this novel approach can best be utilized against melanoma.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3527-3539"},"PeriodicalIF":6.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692020","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":"Macrophage Membrane Coated Manganese Dioxide Nanoparticles Loaded with Rapamycin Alleviate Intestinal Ischemia-Reperfusion Injury by Reducing Oxidative Stress and Enhancing Autophagy.","authors":"Ruxiang Sheng, Wei Wang, Weian Zeng, Bin Li, Haoyuan Yu, Xuan Li, Yanqiu Liang, Ying Wang, Yuhui Liao, Dezhao Liu","doi":"10.2147/IJN.S507546","DOIUrl":"10.2147/IJN.S507546","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia-reperfusion (I/R) injury is a common and severe clinical issue. With high morbidity and mortality, it burdens patients and the healthcare system. Despite the efforts in medical research, current treatment options are unsatisfactory, urging novel therapeutic strategies. Oxidative stress and dysregulated autophagy play pivotal roles in the pathogenesis of I/R injury, damaging intestinal tissues and disrupting normal functions. The aim of this study is to fabricate macrophage membrane-coated manganese dioxide nanospheres loaded with rapamycin [Ma@(MnO₂+RAPA)] for alleviating intestinal I/R injury.</p><p><strong>Methods: </strong>We engineered honeycomb MnO₂ nanospheres coated with a macrophage membrane to act as a drug delivery system, encapsulating RAPA. In vitro OGD/R model in IEC-6 cells and in vivo mouse I/R injury models were used. Targeting ability was evaluated through in-vivo imaging system. Effects on cell viability, reactive oxygen species (ROS) levels, oxygen generation, inflammatory factors, apoptosis, autophagy, and biocompatibility were detected by methods such as MTT assay, fluorescence microscopy, ELISA kit, TUNEL assay, Western blotting and histological analysis.</p><p><strong>Results: </strong>In this study, Ma@(MnO₂+RAPA) efficiently deliver RAPA to damaged tissues and exhibited good ROS-responsive release. Our data showed that Ma@(MnO₂+RAPA) reduced ROS, increased O₂, inhibited inflammation, and promoted autophagy while reducing apoptosis in IEC-6 cells. In a mouse I/R model, Ma@(MnO₂+RAPA) significantly reduced Chiu's score, improved tight conjunction proteins, decreased apoptosis, reduced levels of inflammatory cytokines and oxidative stress. RAPA released from the Ma@(MnO₂+RAPA), enhanced the expression of autophagy-regulated proteins p62, Beclin-1, and LC3II. The biocompatibility and safety of Ma@(MnO₂+RAPA) were confirmed through histological analysis and biochemical detection in mice.</p><p><strong>Conclusion: </strong>Our results demonstrated that Ma@(MnO₂+RAPA) alleviated intestinal I/R injury by reducing oxidative stress, promoting autophagy, and inhibiting inflammation. This study offers a potential therapeutic strategy for the treatment of intestinal ischemia-reperfusion injury.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3541-3557"},"PeriodicalIF":6.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691927","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":"Combined Esculentin-2CHa Fusion Protein-Coated Au Nanoparticles for Effective Against Non-Alcoholic Fatty Liver Disease in Mice Model.","authors":"Reeju Amatya, Amala Joseph, Gu Seob Roh, Cheol Moon, Yassmine Benmokadem, Doyeon Kim, Kyoung Ah Min, Meong Cheol Shin","doi":"10.2147/IJN.S497645","DOIUrl":"10.2147/IJN.S497645","url":null,"abstract":"<p><strong>Introduction: </strong>Extensive research has focused on identifying effective treatments for NAFLD, with numerous bioactive peptide candidates showing significant promise. In this research, a long-acting esculentin-2CHa(1-30)-coated AuNPs (ESC-ABD-AuNPs) was developed and the applicability was evaluated for their use in the treatment of non-alcoholic fatty liver disease (NAFLD).</p><p><strong>Methods: </strong>ESC-ABD-AuNPs were synthesized by adopting a 1-step reduction process and the successful preparation of the nanoparticles (NPs) was assessed by various physical characterizations including transmission electron microscopy (TEM), ultraviolet-visible (UV-VIS) absorption spectra, dynamic light scattering (DLS), and Fourier Transform Infrared Spectroscopy (FT-IR). After the ESC-ABD-AuNPs were prepared, cytotoxicity, pharmacokinetics (PK), and biodistribution profiles were identified. Then, with a high-fat diet (HFD)-fed obese mice model, efficacy studies were carried out focused on their effects for anti-hyperglycemia and anti-NAFLD. Furthermore, the feasibility of loading a small molecule onto the NPs was evaluated for potential combination therapy.</p><p><strong>Results: </strong>ESC-ABD-AuNPs were synthesized with an average hydrodynamic size of 120 (±10) nm and demonstrated good stability and an extended plasma half-life of 28.3 h. The NPs exhibited high liver accumulation and were well tolerated in cell viability tests. In PK and biodistribution studies, ESC-ABD-AuNPs showed prolonged retention in major organs, such as the pancreas and the liver. Therapeutic efficacy was demonstrated in the HFD-fed obese mice, where the ESC-ABD-AuNPs significantly reduced blood glucose levels, improved glucose tolerance, and mitigated liver fat accumulation. The ESC-ABD-AuNPs platform also showed potential for combination therapies, demonstrated by its ability to load obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, found effective for the treatment of NAFLD in clinical studies.</p><p><strong>Conclusion: </strong>Overall, this study has demonstrated the promising potential of ESC-ABD-AuNPs as a novel treatment for NAFLD. This research suggests that ESC-ABD-AuNPs could be a significant advancement in drug delivery and liver disease treatment, particularly for combination therapies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3407-3421"},"PeriodicalIF":6.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692113","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":"Aptamer Functionalized Liposomes Co-Loaded with Exenatide-4 and Coenzyme Q10 Ameliorate Type 2 Diabetes Mellitus by Improving Pancreatic β Cell Function.","authors":"Shangying Xiao, Lei Rao, Canying Yan, Ling Nie, Leiqi Wang, Yingyin Zhao, Shihao Zhang, WeiMao Zhan, Dongyun Qin, Manjiao Zhuang","doi":"10.2147/IJN.S510240","DOIUrl":"10.2147/IJN.S510240","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidative stress has been shown to disrupt β-cell function and promote the development of type 2 diabetes mellitus (T2DM). Exenatide-4 (Ext-4) is a widely used anti-glycemic drug but cannot restore pancreatic β-cells' structure and function. Coenzyme Q10 (CoQ10) has great antioxidant activities but shows suboptimal therapeutic effects because of its poor solubility and poor bioavailability. To further enhance the therapeutic efficacy of the drugs, a pancreas-targeting liposomal co-delivery system encapsulating Ext-4 and CoQ10 ((E+Q)-Lip-Apt) was designed, using the aptamers as the targeting ligands.</p><p><strong>Methods: </strong>(E+Q)-Lip-Apt was prepared by thin film dispersion method and its optimal formulation was obtained through single-factor experiments and orthogonal experiments. The pancreatic β-cell protecting effect of (E+Q)-Lip-Apt was investigated both in vitro and in vivo.</p><p><strong>Results: </strong>(E+Q)-Lip-Apt exhibited uniform size, good dispersion, and high encapsulation efficiency (EE) for both Ext-4 and CoQ10. The in vitro results showed that (E+Q)-Lip-Apt manifested superior capacity in scavenging ROS, enhancing mitochondrial membrane potential, and reducing malondialdehyde (MDA) content compared to Ext-4 in MIN6 cells. In vivo investigations demonstrated that (E+Q)-Lip-Apt significantly improved glucose tolerance, insulin sensitivity, hepatic lipid metabolism, oxidative stress, and enhanced antioxidant enzyme activity in diabetic mice. Moreover, Hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) results indicated that (E+Q)-Lip-Apt could improve liver and pancreatic lesions, restoring the structure and function of β-cells in diabetic mice.</p><p><strong>Conclusion: </strong>(E+Q)-Lip-Apt could improve oxidative stress, thereby restoring pancreatic β-cell function, and alleviating diabetes.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3363-3378"},"PeriodicalIF":6.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692062","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":"Layered Double Hydroxide Nanoparticles Loaded with Resveratrol Inhibit Glycolysis and Show Efficacy in the Treatment of Breast Cancer.","authors":"Chenchen Geng, Liuyang Yan, Yunhao Li, Houcong Li, Yuxin Ji, Yuhan Xiao, Zhifa Wang, Xiaoqi Chen, Changjie Chen, Qingling Yang, Baoding Tang, Wenrui Wang","doi":"10.2147/IJN.S492145","DOIUrl":"10.2147/IJN.S492145","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most common cancers among women. Tumor cell proliferation is highly dependent on aerobic glycolysis, so regulating aerobic glycolysis in breast cancer cells is a promising therapeutic strategy. Resveratrol (Res), as a potential new anti-breast cancer drug, has been shown to regulate the glycolysis of cancer cells and inhibit the metastasis and recurrence of breast cancer. The nano drug delivery system can regulate the aerobic glycolysis metabolism by targeting the signaling factors and reaction products of the tumor aerobic glycolysis process to enhance the anti-tumor effect.</p><p><strong>Methods: </strong>A new albumin-modified layered double hydroxide resveratrol dosage form (BSA@LDHs-Res) was synthesized by hydrothermal co-precipitation. Characterization was carried out to determine the successful synthesis of the nanocarrier system. The bioactivity, glycolytic activity and biocompatibility were examined by in vitro cellular assays; in vivo experiments were performed to further evaluate the anti-tumor effects of the BSA@LDHs-Res dosage form for breast cancer.</p><p><strong>Results: </strong>In this study, we obtained for the first time a bovine serum albumin-modified BSA@LDHs-Res loaded dosage form, which was able to enter breast cancer cells SKBR3 and MDA-MB-231 via endocytosis and successfully escaped from lysosomal capture. BSA@LDHs-Res inhibited the proliferation, migration, and invasion of two types of breast cancer cells, induced apoptosis, and promoted the reduction of mitochondrial membrane potential and ROS. BSA@LDHs-Res inhibited the expression and viability of the key enzymes of glycolysis, hexokinase 2 (HK2), pyruvate kinase (PK), and lactate dehydrogenase, resulting in decreased glucose consumption, decreased lactate accumulation, and decreased intracellular ATP levels. BSA@LDHs-Res was examined in the mouse model with good anti-tumor effects.</p><p><strong>Conclusion: </strong>BSA@LDHs-Res is an efficient nanoreagent for the treatment of breast cancer. The albumin-modified resveratrol layered double hydroxide delivery system developed in this study will provide some theoretical references for further research and clinical application of tumor aerobic glycolysis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3423-3444"},"PeriodicalIF":6.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691922","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}