International Journal of Nanomedicine最新文献

{"title":"Icariin-Enhanced Osteoclast-Derived Exosomes Promote Repair of Infected Bone Defects by Regulating Osteoclast and Osteoblast Communication.","authors":"Yang Zhang, Minjie Zhang, Mengying Li, Maomao Miao, Dan Shou, Peijian Tong","doi":"10.2147/IJN.S483621","DOIUrl":"10.2147/IJN.S483621","url":null,"abstract":"<p><strong>Background: </strong>Infected bone defects pose a challenging clinical issue due to an imbalance of osteoclasts (OC) and osteoblasts (OB). Exosomes are crucial for intercellular signaling of OC and OB in bone repair. Icariin, has been shown to regulate the balance between OC and OB. However, the specific mechanisms by which icariin influences exosomes derived from osteoclasts, and subsequently impacts osteoblast activity, remain unclear. This study aims to investigate the effects of icariin-treated osteoclast-derived exosomes (ICA-OC-Exo) on osteoblast function and bone repair in cases of infected bone defects.</p><p><strong>Methods: </strong>We investigated the exosome profile and localization of multivesicular bodies (MVB) and quantification of intraluminal vesicles (ILVs) in osteoclasts by using transmission electron microscopy. Additionally, the expressions of Rab27A and MITF, which are associated with exosome release, were determined through immunofluorescence staining and Western blot. The profiling of exosomal miRNA expression was conducted via miRNA-sequencing. The effects of ICA-OC-Exo on osteoblast differentiation were determined using RT-qPCR, Western blot, alkaline phosphatase staining. Additionally, ICA-OC-Exo was administered into the localized bone defect of the infected bone rat models, and bone formation was assessed using Micro-CT.</p><p><strong>Results: </strong>Icariin increased the presence of MVBs in the cytoplasm through modulation of the MITF/Rab27A signaling pathway, resulting in higher number of ICA-OC-Exo compared to OC-Exo. Additionally, miR-331-3p expression in ICA-OC-Exo was found to be elevated compared to OC-Exo. ICA-OC-Exo was observed to stimulate osteoblast function by targeting FGF23, reducing DKK1, and subsequently upregulating ALP. In the in vivo study, ICA-OC-Exo exhibited the capacity to enhance bone healing at the site of a local bone defect following anti-infection treatment.</p><p><strong>Conclusion: </strong>Icariin enhanced the quantification of OC-Exo and the expression of miRNA-331-3p in OC-Exo, leading to the regulation of osteoblast function via activation of the miRNA-331-3p/FGF23/DKK1 pathway. ICA-OC-Exo demonstrated potential clinical applicability in bone repair of infected bone defects.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12389-12407"},"PeriodicalIF":6.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716057","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":"Long-Circulating Nanoemulsion with Oxygen and Drug Co-Delivery for Potent Photodynamic/Antibiotic Therapy Against Multidrug-Resistant Gram-Negative Bacterial Infection.","authors":"Xiaolong Li, Xinyi Hou, Siqin Zhang, Jianming Xiong, Yuanyuan Li, Wenjun Miao","doi":"10.2147/IJN.S477278","DOIUrl":"10.2147/IJN.S477278","url":null,"abstract":"<p><strong>Purpose: </strong>Compared to conventional photodynamic therapy (PDT), oxygen-affording PDT represents a promising strategy for treating multidrug-resistant (MDR) gram-negative bacterial infections due to its enhanced sensitization ability towards bacteria and amplified therapeutic efficacy. Over the last decade, various nanoplatforms for the co-delivery of oxygen and photosensitizers have been developed. However, their application in the treatment of infectious diseases is hampered by their poor stability and easy clearance by the reticuloendothelial system (RES).</p><p><strong>Methods: </strong>To address these obstacles, we reported an erythrocyte membrane (EM) camouflaged nanoemulsion containing chlorin e6 (Ce6) and perfluorocarbon (FDC), named ECF, showing good colloidal stability and long-circulating potential, making it suitable for fighting against MDR Gram-negative bacterial infections. The nanoemulsion was fabricated and characterized. The oxygen loading and release performance, photodynamic activity, and bactericidal performance of ECF against <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) were evaluated. Furthermore, the antiphagocytosis profile was tested in vitro using Raw 264.7 cells. In addition, the pharmacokinetic behavior and therapeutic efficiency of ECF were studied in vivo.</p><p><strong>Results: </strong>ECF exhibited superior oxygen loading and release behavior, potent photodynamic activity, and negligible toxicity to mammalian cells. Upon light irradiation, the antibacterial rate of preoxygenated-ECF reached 98% at 40 μg mL^-1 of Ce6 and the bactericidal activity of preoxygenated-ECF and Gen was 3.3 folds higher than that of Gen. Furthermore, ECF could effectively inhibit uptake by phagocytes and circulate in the blood 1.5-fold longer than that of nanoemulsion without EM modification (CF) following intravenous administration. In addition, preoxygenated-ECF combined with antibiotic plus light irradiation showed prominent therapeutic efficacy in treating <i>A. baumannii</i>-induced acute peritonitis, accompanied by good biocompatibility in vivo.</p><p><strong>Conclusion: </strong>Our results provide a novel paradigm for evading immune clearance, prolonging retention time and improving synergetic bactericidal capacity in combination with PDT and antibiotic therapy against planktonic bacteria and gram-negative bacterial infections.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12205-12219"},"PeriodicalIF":6.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716060","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":"A Multifunctional Nanodrug Co-Delivering VEGF-siRNA and Dexamethasone for Synergistic Therapy in Ocular Neovascular Diseases.","authors":"Xiaochen Ma, Yubo Cui, Min Zhang, Qinghua Lyu, Jun Zhao","doi":"10.2147/IJN.S492363","DOIUrl":"10.2147/IJN.S492363","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidant stress, abnormal angiogenesis, and inflammation are three key factors contributing to the development of ocular neovascular diseases (ONDs). This study aims to develop a multifunctional nanodrug, DEX@MPDA-Arg@Si (DMAS), which integrates mesoporous polydopamine, vascular endothelial growth factor (VEGF)-siRNA, and dexamethasone (DEX) to address these therapeutic targets.</p><p><strong>Methods: </strong>Physicochemical properties of DMAS were measured using transmission electron microscopy and a nanoparticle size analyzer. The encapsulation efficiency and drug loading capacity of DMAS were measured using a UV-visible spectrophotometer. The in vivo therapeutic efficacy and ocular safety of DMAS were evaluated using three established mouse models, including the alkali burn-induced corneal neovascularization (CoNV) model, the oxygen-induced retinopathy (OIR) model, and the laser-induced choroidal neovascularization (CNV) model.</p><p><strong>Results: </strong>The DMAS nanoparticles demonstrated a uniform bowl-like shape with an average size of 264.9 ± 2.5 nm and a zeta potential of -28.2 ± 4.2 mV. They exhibited high drug-loading efficiency (36.04 ± 3.60% for DEX) and excellent biocompatibility. In vitro studies confirmed its potent antioxidant, anti-inflammatory, and anti-apoptotic properties. In vivo, DMAS treatment led to significant therapeutic effects across all models. It effectively inhibited CoNV, promoted corneal repair, and modulated inflammation in the alkali burn model. In the OIR model, DMAS reduced retinal neovascularization by decreasing VEGF expression. In the laser-induced CNV model, it significantly reduced the CNV area and lesion thickness.</p><p><strong>Conclusion: </strong>This research developed a multifunctional nanodrug, DMAS, capable of co-delivering VEGF-siRNA and DEX, offering synergistic therapeutic benefits for treating ONDs. The DMAS nanodrug demonstrates promising anti-inflammatory, antioxidative, and anti-angiogenic effects, highlighting its potential as a versatile and effective treatment for multiple ocular conditions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12369-12387"},"PeriodicalIF":6.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739334","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":"Enhancing Transfection Efficacy in Glioma Cells: A Comparison of Microfluidic <i>versus</i> Manual Polypropylenimine Dendriplex Formation.","authors":"Hawraa Ali-Jerman, Zainab Al-Quraishi, Ashish Muglikar, Yvonne Perrie, Rothwelle J Tate, Margaret Mullin, Gayle McNeill, Graeme Mackenzie, Christine Dufès","doi":"10.2147/IJN.S490936","DOIUrl":"10.2147/IJN.S490936","url":null,"abstract":"<p><strong>Background: </strong>Gene therapy is a promising therapeutic approach for treating various disorders by introducing modified nucleic acids to correct cellular dysfunctions or introduce new functions. Despite significant advancements in the field, the effective delivery of nucleic acids remains a challenge, due to biological barriers and the immune system's ability to target and destroy these molecules. Due to their branched structure and ability to condense negatively charged nucleic acids, cationic dendrimers have shown potential in overcoming these challenges. Despite this, standardized scalable production methods are still lacking. This study investigates the use of microfluidics to formulate generation 3-diaminobutyric polypropylenimine (DAB) dendriplexes and compares their characteristics and in vitro gene delivery efficacy to those prepared using conventional manual mixing.</p><p><strong>Methods: </strong>DAB dendriplexes were produced by both microfluidic and manual approaches and characterized. Their cellular uptake and gene expression were evaluated on C6 glioma cancer cells in vitro.</p><p><strong>Results: </strong>Dendriplexes formed using microfluidics at the optimal flow rate and ratio demonstrated enhanced DNA condensation over time, achieving up to 97% condensation at 24 hours. Both preparation methods produced positively charged dendriplexes, indicating stable formulations. However, dendriplexes prepared through hand mixing resulted in smaller particle sizes, significantly higher cellular uptake and gene expression efficacy compared to those prepared by microfluidics. Nonetheless, microfluidic preparation offers the advantage of standardized and scalable production, which is essential for future applications.</p><p><strong>Conclusion: </strong>This study highlights the potential of microfluidic technology to improve precision and scalability in gene delivery, paving the way for future advancements in gene therapy. Our findings suggest that, with further optimization, microfluidic systems could provide superior control over dendriplex formation, expanding their potential use in gene therapy applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12189-12203"},"PeriodicalIF":6.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715997","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":"Nose to Brain: Exploring the Progress of Intranasal Delivery of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers.","authors":"Yang Zheng, Limei Cui, Haoran Lu, Zhen Liu, Zhaoxue Zhai, Huikang Wang, Liting Shao, Zhaoyang Lu, Xicheng Song, Yu Zhang","doi":"10.2147/IJN.S497480","DOIUrl":"10.2147/IJN.S497480","url":null,"abstract":"<p><p>The intranasal (IN) route of drug delivery can effectively penetrate the blood-brain barrier and deliver drugs directly to the brain for the treatment of central nervous system (CNS) disorders via intra-neuronal or extra-neuronal pathways. This approach has several advantages, including avoidance of first-pass metabolism, high bioavailability, ease of administration, and improved patient compliance. In recent years, an increasing number of studies have been conducted using drugs encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and delivering them to the brain via the IN pathway. SLNs are the first-generation solid lipid nanocarriers, known for their excellent biocompatibility, high drug-loading capacity, and remarkable stability. NLCs, regarded as the second-generation SLNs, not only retain the advantages of SLNs but also exhibit enhanced stability, effectively preventing drug leakage during storage. In this review, we examined in vivo studies conducted between 2019 and 2024 that used SLNs and NLCs to address CNS disorders via the IN route. By using statistical methods to evaluate pharmacokinetic parameters, we found that IN delivery of SLNs and NLCs markedly enhanced drug accumulation and targeting within the brain. Additionally, pharmacodynamic evaluations indicated that this delivery method substantially improved the therapeutic effectiveness of the drugs in alleviating symptoms in rat models of CNS diseases. In addition, methods for enhancing the efficacy of nose-to-brain delivery of SLNs and NLCs are discussed, as well as advances in clinical trials regarding SLNs and NLCs.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12343-12368"},"PeriodicalIF":6.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739317","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":"SFRP1-Silencing GapmeR-Loaded Lipid-Polymer Hybrid Nanoparticles for Bone Regeneration in Osteoporosis: Effect of Dosing and Targeting Strategy.","authors":"Erik Briffault, Ricardo Reyes, Patricia Garcia-Garcia, Helena Rouco, Luis Diaz-Gomez, Maria Rosa Arnau, Carmen Evora, Patricia Diaz-Rodriguez, Araceli Delgado","doi":"10.2147/IJN.S476546","DOIUrl":"10.2147/IJN.S476546","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoporosis is a metabolic disorder characterized by the loss of bone mass and density. Nucleic acid-based therapies are among the most innovative approaches for osteoporosis management, although their effective delivery to bone tissue remains a challenge. In this work, SFRP1-silencing GampeR loaded-nanoparticles were prepared and functionalized with specific moieties to improve bone targeting and, consequently, therapeutic efficacy. SFRP1-silencing would promote osteoblastic differentiation by enhancing the WNT/β-catenin pathway and thus diminishing the progression of osteoporosis.</p><p><strong>Methods: </strong>A nucleic acid-based delivery system consisting of lipid-polymer hybrid nanoparticles (LPNPs) loading a GapmeR for SFRP1 silencing was developed and further functionalized with two bone-targeting moieties: a specific aptamer (Apt) for murine mesenchymal stem cells and an antiresorptive drug, namely alendronate (ALD). These systems were tested in vivo in osteoporotic mice at different dosage regimens to analyze dose dependence in bone-forming activity and potential toxicity. The quality of trabecular and cortical bone was assessed by both micro computed tomography (micro-CT) and histological and histomorphometric analyses. Early and late osteogenesis were quantified by immunohistochemistry.</p><p><strong>Results: </strong>Results showed that functionalizing LPNPs loaded with an SFRP1-silencing GapmeR using both Apt and ALD improved bone quality and enhanced osteogenesis following a dose-effect relationship, as revealed by micro-CT, histological and immunohistochemical analyses. In contrast, non-functionalized LPNPs did not produce these effects.</p><p><strong>Conclusion: </strong>These findings highlight the relevance of proper targeting and dosage in nucleic acid-based therapeutics, proving to be crucial for exerting their therapeutic effect: a deficient targeting strategy and/or dosage may result in the therapeutic failure of an adequate gene therapy agent.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12171-12188"},"PeriodicalIF":6.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716062","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 New Era of Neural Modulation Led by Smart Nanomaterials.","authors":"Zhitao Hou","doi":"10.2147/IJN.S491440","DOIUrl":"10.2147/IJN.S491440","url":null,"abstract":"<p><p>Understanding the physiology and pathology of neural circuits is crucial in neuroscience research. A variety of techniques have been utilized in medical research, with several established methods applied in clinical therapy to enhance patient' neurological functions. Traditional methods include generating electric fields near neural tissue using electrodes, or non-contact modulation using light, chemicals, magnetic fields, and ultrasound. The advent of nanotechnology represents a new advancement in neural modulation techniques, offering high precision and the ability to target specific cell types. Smart nanomaterials enable the conversion of remote signals (such as light, magnetic, or ultrasound) into local stimuli (eg, electric fields or heat) for neurons. Surface treatment technologies of nanomaterials have enhanced biocompatibility, making targeted delivery to specific cell types possible and paving the way for precise neural modulation. This perspective will explore neural modulation techniques supported by nanomedical materials, focusing on photoelectric, photothermal, magnetoelectric, magnetothermal, and acoustoelectric conversion mechanisms, and looking forward to their medical applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12287-12295"},"PeriodicalIF":6.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716064","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 sgc8-Modified PAMAM Nanoparticles for Targeted siRNA Delivery to Inhibit BCL11B in T-Cell Acute Lymphoblastic Leukemia.","authors":"Xiangbo Zeng, Dingrui Nie, Zhen Liu, Xueting Peng, Xianfeng Wang, Kangjie Qiu, Shuxin Zhong, Ziwei Liao, Xianfeng Zha, Yangqiu Li, Chengwu Zeng","doi":"10.2147/IJN.S477597","DOIUrl":"10.2147/IJN.S477597","url":null,"abstract":"<p><strong>Introduction: </strong>T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease with limited targeted therapy options. Overexpression of B-cell lymphoma/leukemia 11B is frequently observed in T-ALL and contributes to leukemogenesis. Knockdown of BCL11B inhibits T-ALL cell proliferation and induces apoptosis, making it a potential therapeutic target. However, the clinical application of siRNA therapies is hindered by challenges such as poor delivery efficiency and limited clinical outcomes.</p><p><strong>Methods: </strong>We developed a targeted delivery system for BCL11B siRNA (siBCL11B) using generation 5 polyamidoamine (G5-PAMAM) dendrimers conjugated with the sgc8 aptamer, which specifically binds to the T-ALL cell membrane protein PTK7. This nanoparticle, designated G5-sgc8-siBCL11B, was designed to selectively deliver siRNA to T-ALL cells. In vitro and in vivo experiments were conducted to evaluate its therapeutic efficacy and safety.</p><p><strong>Results: </strong>We demonstrate that sgc8-conjugated siBCL11B nanoparticles selectively and efficiently target BCL11B-overexpressing T-ALL cells, significantly inhibiting cell viability and promoting apoptosis while exhibiting minimal impact on the viability of normal T cells. In T-ALL mouse model studies, G5-sgc8-siBCL11B and G5-siBCL11B significantly inhibited the progression of T-ALL in vivo, extending the survival of mice compared to the control (CTR), G5, and G5-sgc8 groups. Although there was no significant difference in survival between the G5-sgc8-siBCL11B and G5-siBCL11B groups, a trend towards improved survival was observed (p = 0.0993).</p><p><strong>Conclusion: </strong>The G5-sgc8-siBCL11B nanoparticle system demonstrated efficient delivery and significant therapeutic efficacy, highlighting its potential as a promising novel approach for the treatment of T-ALL.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12297-12309"},"PeriodicalIF":6.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710112","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":"Hybrid Biosilica Nanoparticles for in-vivo Targeted Inhibition of Colorectal Cancer Growth and Label-Free Imaging.","authors":"Donatella Delle Cave, Maria Mangini, Chiara Tramontano, Luca De Stefano, Marco Corona, Ilaria Rea, Anna Chiara De Luca, Enza Lonardo","doi":"10.2147/IJN.S480168","DOIUrl":"10.2147/IJN.S480168","url":null,"abstract":"<p><strong>Background: </strong>Metastasis-initiating cells are key players in progression, resistance, and relapse of colorectal cancer (CRC), by leveraging the regulatory relationship between Transforming Growth Factor-beta (TGF-β) signaling and anti-L1 cell adhesion molecule (L1CAM).</p><p><strong>Methods: </strong>This study introduces a novel strategy for CRC targeted therapy and imaging based on the use of a hybrid nanosystem made of gold nanoparticles-covered porous biosilica further modified with the (L1CAM) antibody.</p><p><strong>Results: </strong>The nanosystem intracellularly delivers galunisertib (LY), a TGF-β inhibitor, aiming to inhibit epithelial-mesenchymal transition (EMT), a process pivotal for metastasis. Anti-L1CAM antibody-functionalized nanoparticles (NPs) target tumor-initiating cells expressing L1CAM, inhibiting cancer growth. The number of antibody molecules conjugated to the single NP is precisely quantified, revealing a high surface coverage that facilitates the tumor targeting. The therapeutic efficacy of the nanosystem is investigated in organoid-like cultures of CRC cells and in vivo mouse models, showing a significant reduction in tumor growth. The spatial distribution of NPs within CRC tumors from mice is investigated using a label-free optical approach based on Raman micro-spectroscopy.</p><p><strong>Conclusion: </strong>This research highlights the multifunctional capabilities of engineered biosilica NPs, which offer new insights in targeted CRC therapy and imaging, improving patient outcomes and paving the way for personalized therapies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12079-12098"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710060","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":"Toxicity and Oxidative Stress Biomarkers in the Organs of Mice Treated with Mesoporous Polydopamine Nanoparticles Modified with Iron and Coated with Cancer Cell Membrane.","authors":"Marta Szukalska, Bartosz F Grześkowiak, Magdalena J Bigaj-Józefowska, Marta Witkowska, Emilia Cicha, Patrycja Sujka-Kordowska, Izabela Miechowicz, Michał Nowicki, Radosław Mrówczyński, Ewa Florek","doi":"10.2147/IJN.S481120","DOIUrl":"10.2147/IJN.S481120","url":null,"abstract":"<p><strong>Purpose: </strong>Polydopamine nanoparticles (PDA NPs) have great potential in medicine. Their applications being widely investigated in cancer therapy, imaging, chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and tissue repair. The aim of our study was to assess the in vivo toxicity and changes in oxidative stress biomarkers in organs of animals treated with mesoporous PDA NPs modified with iron (MPDAFe NPs), coated with the cancer cell membrane and loaded with doxorubicin (DOX), and subsequently subjected to PTT.</p><p><strong>Methods: </strong>Liver and kidney homogenates were obtained from BALB/c nude mice with xenograft HepG2 human hepatoma cells, treated with iron modified mesoporous PDA nanoparticles, coated with the cancer cell membrane and loaded with doxorubicin (MPDAFe@DOX@Mem NPs), and subjected to PTT. These samples were used for histological evaluation and measurement of oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD).</p><p><strong>Results: </strong>In the kidney, MPDAFe@DOX@Mem NPs in combination with PTT increased GSH (43%), TBARS (32%), and CAT (27%), while SOD decreased by 20% compared to the control group. Additionally, CAT activity in the liver increased by 79%.</p><p><strong>Conclusion: </strong>Significant differences in oxidative stress parameters and histological changes after administration with MPDAFe@DOX@Mem NPs and PTT were observed in the kidneys, showing more pronounced changes than the liver, indicating potential kidney toxicity. Our research provides insights into oxidative stress and possible toxic effects after in vivo administration of mesoporous PDA NPs combined with chemotherapy-photothermal therapy (CT-PTT), which is extremely important for their future applications in anticancer therapies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12053-12078"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710153","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}