International Journal of Nanomedicine最新文献

{"title":"Chitosan-Based Nanoparticles Targeted Delivery System: In Treatment Approach for Dyslipidemia.","authors":"Yedi Herdiana, Jutti Levita, Supat Jiranusornkul","doi":"10.2147/IJN.S517492","DOIUrl":"10.2147/IJN.S517492","url":null,"abstract":"<p><p>Hyperlipidemia, characterized by abnormally high lipid levels in the bloodstream, is a significant risk factor for cardiovascular diseases. Conventional treatments have limitations in efficacy and may lead to side effects. Nanotechnology offers unique advantages in drug delivery, including improved drug stability, prolonged circulation time, and enhanced tissue targeting. Using nanoparticles as carriers, therapeutic agents can be precisely delivered to the target site, such as the liver or arterial walls, where lipid metabolism occurs. Chitosan nanoparticles represent an advanced approach engineered with precision to target atherosclerotic plaques. They have dual functionalities, serving therapeutic and diagnostic purposes in managing atherosclerosis. Targeting strategies involve coating nanoparticles with ligands or antibodies that recognize specific receptors overexpressed in hyperlipidemic conditions. This selective uptake maximizes the therapeutic effect while minimizing off-target effects, making it a promising alternative to traditional treatments. The review provides an overview of recent research developments for managing dyslipidemia based on the molecular target pathway of dyslipidemia, focusing on Chitosan-based delivery systems that allow controlled drug release, targeting, and enhancing patient compliance.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6611-6636"},"PeriodicalIF":6.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173788","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":"Selective Glycopolymer Inhibitors of Galectin-3: Supportive Anti-Cancer Agents Protecting Monocytes and Preserving Interferon-Gamma Function.","authors":"Marcela Filipová, Marina Rodrigues Tavares, Michaela Hovorková, Viktoria Heine, Pavlína Nekvasilová, Vladimír Křen, Tomáš Etrych, Petr Chytil, Pavla Bojarová","doi":"10.2147/IJN.S503381","DOIUrl":"10.2147/IJN.S503381","url":null,"abstract":"<p><strong>Introduction: </strong>The immunosuppressive roles of galectin-3 (Gal-3) in carcinogenesis make this lectin an attractive target for pharmacological inhibition in immunotherapy. Although current clinical immunotherapies appear promising in the treatment of solid tumors, their efficacy is significantly weakened by the hostile immunosuppressive tumor microenvironment (TME). Gal-3, a prominent TME modulator, efficiently subverts the elimination of cancer, either directly by inducing apoptosis of immune cells or indirectly by binding essential effector molecules, such as interferon-gamma (IFNγ).</p><p><strong>Methods: </strong><i>N</i>-(2-Hydroxypropyl)methacrylamide (HPMA)-based glycopolymers bearing poly-<i>N</i>-acetyllactosamine-derived tetrasaccharide ligands of Gal-3 were designed, synthesized, and characterized using high-performance liquid chromatography, dynamic light scattering, UV-Vis spectrophotometry, gel permeation chromatography, nuclear magnetic resonance, high-resolution mass spectrometry and CCK-8 assay for evaluation of glycopolymer non-toxicity. Pro-immunogenic effects of purified glycopolymers were tested by apoptotic assay using flow cytometry, competitive ELISA, and in vitro cell-free INFγ-based assay.</p><p><strong>Results: </strong>All tested glycopolymers completely inhibited Gal-3-induced apoptosis of monocytes/macrophages, of which the M1 subtype is responsible for eliminating cancer cells during immunotherapy. Moreover, the glycopolymers suppressed Gal-3-induced capture of glycosylated IFNγ by competitive inhibition to Gal-3 carbohydrate recognition domain (CRD), which enables further inherent biological activities of this effector, such as differentiation of monocytes into M1 macrophages and repolarization of M2-macrophages to the M1 state.</p><p><strong>Conclusion: </strong>The prepared glycopolymers are promising inhibitors of Gal-3 and may serve as important supportive anti-cancer nanosystems enabling the infiltration of proinflammatory macrophages and the reprogramming of unwanted M2 macrophages into the M1 subtype.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6591-6609"},"PeriodicalIF":6.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173792","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":"Lipid-Coated Ag@MnO₂ Core-Shell Nanoparticles for Co-Delivery of Survivin siRNA in Breast Tumor Therapy.","authors":"Jing Zhang, Min Zha, Shanghua Xiao, Nina Filipczak, Satya Siva Kishan Yalamarty, Xiangping Wu, Chenkai Gong, Xiang Li","doi":"10.2147/IJN.S510514","DOIUrl":"10.2147/IJN.S510514","url":null,"abstract":"<p><strong>Objective: </strong>Nanoparticles constructed with silver/manganese dioxide (Ag@MnO₂) as the core, in conjunction with survivin siRNA (sis) and cyclo(RGD-DPhe-K) (Ag@MnO₂-sis-c-L), were prepared for integrated tumor diagnosis and therapy.</p><p><strong>Methods: </strong>Ag@MnO₂-sis-c-L particles were prepared and characterized. The silver and manganese content were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES). The stability of sis in the system was evaluated by incubation with 50% FBS before the agarose gel electrophoresis experiment. The in vitro photothermal conversion ability, cytotoxicity to 4T1 cells, and cellular uptake of preparations were evaluated. The dialysis technique was employed to determine the in vitro release profile of Ag and Mn from Ag@MnO₂-sis-c-L under various pH conditions. The pharmacokinetic behavior and tissue distribution of silver in vivo were detected by ICP-OES. Animal model experiments were conducted to further evaluate the anti-tumor efficacy of Ag@MnO₂-sis-c-L against breast cancer in combination with infrared irradiation.</p><p><strong>Results: </strong>Our newly synthesized Ag@MnO₂-sis-c-L nanoparticles displayed superior physicochemical properties. The combined application of these nanoparticles with photothermal therapy (PTT) exerted the strongest synergistic inhibitory effects on tumor growth. Survivin protein expression in tumor tissues were markedly suppressed following delivery of nanoparticles loaded with sis. Additionally, magnetic resonance imaging revealed the high imaging capability of hybrid nanoparticles.</p><p><strong>Conclusion: </strong>This study supports the potential utility of Ag@MnO₂-sis-c-L coupled with PTT in therapeutic and diagnostic imaging applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6515-6531"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158571","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":"Advanced Strategies for Ultrasound Control and Applications in Sonogenetics and Gas Vesicle-Based Technologies: A Review.","authors":"Jinpeng Du, Min Liao, Daimo Zhang, Xiangnan Li","doi":"10.2147/IJN.S507322","DOIUrl":"10.2147/IJN.S507322","url":null,"abstract":"<p><p>Control systems play an important role in the diagnosis and treatment of medicine. In contrast to light and magnetic fields, ultrasound has received much attention due to its non-invasive, cost-effective, convenient, and high spatiotemporal precision and deep-penetration characteristics. Some studies have developed special nanomaterials for therapy by controlling the production of reactive oxygen species through ultrasound irradiation. However, the complex functionalities and toxicity issues associated with these nanomaterials limit the development of ultrasound control systems. To overcome these challenges, ultrasound control systems based on synthetic biology have been developed, especially for sonogenetics and gas vesicles. The tunable thermal and mechanical effects of ultrasound act as the main triggering source, enabling engineered cells to perform sono-thermal or sono-mechanical genetic modifications in the targeted tissue. Based on an in-depth understanding of the relationship between ultrasound effects and the design, composition, and applications of engineered cellular technologies, in this review, we focus on recent activation strategies of ultrasound for sonogenetics and gas vesicles, including sono-thermal promoter switch, sono-thermal transient receptor potential channel, sono-mechanical activation and gas vesicles. In addition, applications of these advanced ultrasound control systems for cancer therapy, neural activity, visual recovery and functional imaging are presented. Finally, we discuss the current challenges faced and provide an outlook on the future developments in this evolving field.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6533-6549"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158550","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":"Preparation, and ex vivo and in vivo Characterization of Favipiravir-Loaded Aspasomes and Niosomes for Nose-to-Brain Administration.","authors":"Maryana Salamah, Balázs Volk, István Lekli, István Bak, Alexandra Gyöngyösi, Gábor Kozma, Zoltán Kónya, Ágnes Szalenkó-Tőkés, Ágnes Kiricsi, László Rovó, Diána Balogh-Weiser, István Zupkó, Ildikó Csóka, Gábor Katona, György Tibor Balogh","doi":"10.2147/IJN.S518486","DOIUrl":"10.2147/IJN.S518486","url":null,"abstract":"<p><strong>Purpose: </strong>The present study aimed to develop and compare the intranasal applicability of favipiravir-loaded aspasomes (FAV-ASPs) using film hydration method, and favipiravir-loaded niosomes (FAV-NIOs) using ethanol injection method.</p><p><strong>Methods: </strong>The FAV-ASP and FAV-NIO formulations were characterized according to nanoparticulate characteristics (DLS, drug loading, drug encapsulation efficacy, droplet size distribution), drug release and permeability behavior.</p><p><strong>Results: </strong>The optimized FAV-ASP formulation (FAV-ASP8) consisted of FAV, ascorbyl palmitate, Span® 60 and cholesterol (30:25:25:50 w/w) with nano-scale size range (292.06 ± 2.10 nm), narrow polydispersity index (PDI) value (0.36 ± 0.03), adequate zeta potential (-74.73 ± 3.28 mV) and acceptable encapsulation efficiency (55.33 ± 0.41%). The optimized FAV-NIO formulation (FAV-NIO9) contained FAV, Span® 60 and cholesterol (30:30:40 <i>w/w</i>) with nano-scale size range (167.13 ± 1.60 nm), narrow PDI value (0.07 ± 0.01), adequate zeta potential (-27.1 ± 1.24 mV) and acceptable encapsulation efficiency (51.30 ± 0.69%). FAV-ASP8 and FAV-NIO9 were suitable for spraying into the nasal cavity (droplet size distribution <200 µm). In vitro drug release and permeability studies demonstrated enhanced solubility and increased blood-brain barrier (BBB) permeability of FAV formulations, respectively. The ex vivo human nasal permeability study revealed that FAV diffusion from FAV-ASP8 was higher than from FAV-NIO9 or initial FAV. Furthermore, the in vivo animal study showed that FAV-ASP8 had a higher BBB penetration compared to FAV-NIO9 and pure FAV. The in vitro-in vivo correlation study showed good correlation between the in vitro and the in vivo pharmacokinetic data.</p><p><strong>Conclusion: </strong>FAV-ASP8 for nose-to-brain delivery system could be a promising formulation to improve FAV bioavailability compared to FAV-NIO9.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6489-6514"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150409","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":"Itraconazole Loaded Micelle Based on Methoxy Poly(Ethylene Glycol)-Poly(D, L-Lactic Acid) for Ocular Drug Delivery: In vitro and in vivo Evaluation.","authors":"Jijun He, Jingjing Yang, Zhen Liang, Zhen Zhang, Guojuan Pu, Fudan Dong, Ping Lu, Huiyun Xia, Junjie Zhang","doi":"10.2147/IJN.S521127","DOIUrl":"10.2147/IJN.S521127","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop itraconazole (ITZ)-loaded polymer micelles using methoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PDLLA) as a carrier to improve the ocular bioavailability of ITZ after topical administration.</p><p><strong>Methods: </strong>ITZ-loaded mPEG-PDLLA micelles (ITZ-M) were prepared using the thin-film dispersion method and were characterized by droplet size (DS), zeta potential (ZP), polydispersity index (PDI), morphology, entrapment efficiency (EE%), and critical micelle concentration (CMC). In vitro drug release from ITZ-M, the storage stability and cytotoxicity in human corneal epithelial cells (HCECs) were studied. In vivo transcorneal permeation of micelles labeled with coumarin 6 (C6) was observed using two-photon confocal microscopy, in vivo ocular irritation and pharmacokinetics in rabbit eyes were investigated.</p><p><strong>Results: </strong>The ITZ-Ms were uniform spherical particles with DS of 18.79 ± 0.16 nm and narrow distribution (PDI of 0.037 ± 0.019), the EE% was nearly 100%, and the CMC of the micelles was 0.083mM. Approximately 60% of the drug was released from the ITZ-M within 72 h, which was significantly higher than that released from the ITZ suspension. The results of the stability study and cytotoxicity assays demonstrated that ITZ-M possessed good physical stability at 4°C and have no toxicity to HCECs. Transcorneal studies indicated that the fluorescence intensity (FI) was mostly enriched in the corneal epithelium, which was reduced in the stroma. The FI in the epithelium and stroma for C6 micelles was much stronger than that in the C6 suspension. Ocular irritation evaluation revealed that ITZ-M was well tolerated. Ocular pharmacokinetic analysis indicated that the area under the curve (AUC_0-240min) values in the cornea and conjunctiva of rabbit eyes treated with ITZ-M were approximately 410.9- and 2.3-fold higher, respectively, than those treated with ITZ suspension.</p><p><strong>Conclusion: </strong>This study provides a potential formulation of ITZ for the treatment of fungal keratitis with good tolerability and improved ocular bioavailability.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6447-6462"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150406","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":"Polymeric Nanomedicines in Diabetic Wound Healing: Applications and Future Perspectives.","authors":"Zeyao Chen, Kakei Chan, Xin Li, Li Gong, Yingjie Ma, Chiwen Huang, Yan Lu, Li Wang, Chunli Piao","doi":"10.2147/IJN.S514000","DOIUrl":"10.2147/IJN.S514000","url":null,"abstract":"<p><p>The management of diabetic wound continues to pose significant clinical obstacles, primarily attributed to bacterial infections, excessive inflammation, oxidative stress, and impaired angiogenesis. These pathological factors not only severely affect patient well-being but also create considerable burden on medical services. Current managements often show limited efficacy, necessitating the exploration of alternative therapeutic strategies. Polymeric nanomedicines (PNs), owing to their nanoscale properties, enhanced cellular uptake, stability, bioavailability, and biocompatibility, have been broadly utilized for diabetic wound treatment. PNs demonstrate remarkable capabilities in microbial inhibition, inflammation regulation, oxidative stress mitigation, and vascular network formation, particularly when combined with various agents, including organic substances (eg, exosomes), inorganic substances (eg, metals), and biomaterials (eg, chitosan, hyaluronic acid, and hydrogels). This article systematically examines recent progress in PN-based interventions for diabetic wound recovery, highlighting the pivotal role of PNs in mitigating bacterial infection, modulating inflammatory responses, and promoting cellular regeneration. Additionally, we provide a novel perspective on the multifunctionality of PNs and their potential for overcoming the limitations of conventional therapies. Overall, PNs represent an innovative and promising approach to diabetic wound management, outperforming conventional therapies in stability, targeted delivery, and multifunctionality. In the future, investigations should concentrate on refining PNs formulations and administration strategies so as to enhance biocompatibility, and conducting well-designed clinical trials to validate their therapeutic efficacy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6423-6446"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150407","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":"Silk Biowaste Protein Mediated Silver Nanoparticles Synthesis and Analysis of Anti-Inflammatory, Wound Healing, Antidiabetic, Antioxidant, Tyrosinase Inhibition, and Antibacterial Mechanism of Action.","authors":"Gitishree Das, Han-Seung Shin, In-Jun Yang, Ly Thi Huong Nguyen, Jayanta Kumar Patra","doi":"10.2147/IJN.S512524","DOIUrl":"10.2147/IJN.S512524","url":null,"abstract":"<p><strong>Background: </strong>Silk, a natural biowaste protein from silkworm cocoons called sericin, has promising properties as a biomaterial for several biomedical applications, owing to its excellent biocompatibility, biodegradability, hydrophilicity, and reactivity.</p><p><strong>Purpose: </strong>The synthesis of AgNPs using these biowaste protein materials is more efficient, environmentally friendly, and cost-effective.</p><p><strong>Methods: </strong>In this study, a novel approach was developed to synthesize silver nanoparticles (Scn-AgNPs) using sericin as a reducing agent and to study their anti-inflammatory, wound healing, antidiabetic, antioxidant, tyrosinase inhibitory, and antibacterial mechanisms of action.</p><p><strong>Results: </strong>The initial production of Scn-AgNPs was established by a visual color change to brown, followed by UV-visible spectroscopy, which showed a solid absorption band at 422 nm due to surface plasmon resonance. The mean particle size 82.77 nm with a polydispersity index of 0.387, and -30.8 mV zeta potential specifies the strong stability of the nanoparticles. Scn-AgNPs demonstrated promising wound healing potential, with around 67.72% of wound closure rate at 25 µg/mL concentration. Besides, It also displayed significant anti-inflammatory, antioxidant (in terms of DPPH (75.48%), ABTS (95.04%), SOD (73.92%) potential), antidiabetic properties (95.32% of α-amylase inhibition and 94.42% of α-glucosidase inhibition), and tyrosinase inhibition (27.07%) potentials. Furthermore, the Scn-AgNPs also exhibited significant antibacterial potential with the inhibition zones diameter ranging from 13.84 to 16.90 mm against all the three tested bacteria.</p><p><strong>Conclusion: </strong>The results indicated that Scn-AgNPs could be a potential candidate for various applications, including cosmetics for preparing antioxidant rich gels and nano formulations, in the biomedical field as a component of wound dressing, antibacterial dressing, drug carriers and drug delivery systems, and in environmental sectors as antibacterial agents, food packaging, food additives and in vitro/in vivo monitoring. This study highlights the use of sericin bio-waste materials into valuable resources, endorsing sustainability and enhancing the commercial value of silk-based bio-waste materials.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6551-6571"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150419","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":"Brain Delivery Strategies for Biomacromolecular Drugs: Intranasal Administration.","authors":"Huanhuan Wu, Chenyu Li, Hong Yuan, Jingyuan Zhao, Shuai Li","doi":"10.2147/IJN.S520768","DOIUrl":"10.2147/IJN.S520768","url":null,"abstract":"<p><p>Macromolecular Drugs (including monoclonal antibodies, recombinant proteins, and nucleic acid therapies) have become a cornerstone strategy for intervening in complex pathological mechanisms such as cancer, autoimmune diseases, and genetic disorders due to their high specificity for disease targets and low off-target toxicity. However, compared to traditional small-molecule drugs, the high molecular weight (>10 kDa) and structural complexity of macromolecular drugs result in extremely low transmembrane permeability. This is particularly challenging in the treatment of central nervous system (CNS) diseases, where the blood-brain barrier (BBB) imposes stringent selectivity, further limiting drug delivery efficiency. This review focuses on the breakthrough strategy of nose-to-brain (NtB) drug delivery. On one hand, the NtB pathway bypasses the BBB, enabling direct CNS drug delivery. On the other hand, nanocarrier technology can synergistically achieve systemic delivery and brain-targeted transport. Based on the latest research advances, this article systematically examines the feasibility of delivering macromolecular drugs via NtB administration. We comprehensively summarize relevant delivery carriers and discuss the potential advantages of intranasal-brain delivery for CNS disease treatment. Notably, while significant progress has been made in this field, further exploration is still needed regarding the mechanisms of NtB delivery and challenges in clinical translation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6463-6487"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150405","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":"Engineered <i>E. coli</i> OMVs Carrying the Membrane-Binding hGC33 Fragment Precisely Target Liver Cancer and Effectively Treat Tumor.","authors":"Yufei Deng, Bangya Yang, Zelan Yang, Hanyu Xiao, Yan Zou, Cheng Zou, Song Yang, Xi Sun, Yiting Wang, Jin Bai, Liaoqiong Fang, Zhibiao Wang","doi":"10.2147/IJN.S513508","DOIUrl":"10.2147/IJN.S513508","url":null,"abstract":"<p><strong>Background: </strong>Glypican-3 (GPC3), which is a membrane-associated antigen that is overexpressed in hepatocellular carcinoma (HCC). hGC33, a humanized anti-GPC3 antibody, has been validated as a potential antibody drug with good antitumor activity by preclinical studies and the Phase II clinical trial. However, free drug usually lack good tumor penetration. Outer membrane vesicles (OMVs) that are secreted by <i>Escherichia coli</i> function as natural vectors for molecule delivery and mediators of biological signals across tissues. Our study aimed to engineer <i>E. coli</i> for use as a platform to precisely deliver the hGC33 single-chain variable fragment (hGC33-scFv) for the targeted treatment of HCC.</p><p><strong>Methods: </strong>In this study, we utilized <i>E. coli BL21(DE3)</i> to express Hbp-hGC33-scFv fusion protein and generated <i>E. coli</i> hGC33-OMVs. After isolation and characterization, we assessed their chemotaxis toward HepG2  cells by Transwell, coimmunoprecipitation (co-IP) to confirm hGC33-GPC3 binding, and immunofluorescence (IF) to evaluate the localization of hGC33 on OMV membranes. The in vivo efficacy was assessed in BALB/c nude mice harboring HepG2  cell-derived xenografts, and tumor targeting was analyzed with Cy7-labeled OMVs and live imaging. Proliferation assays, cell cycle analysis, and Wnt pathway expression analysis were performed to elucidate the underlying mechanisms.</p><p><strong>Results: </strong>hGC33-OMVs exhibited spherical bilayered nanostructures and displayed hGC33-scFv on their surface. hGC33-OMVs preferentially accumulated in tumors, significantly reducing tumor volume compared with controls and downregulating the proliferation markers Ki67 and PCNA. Transwell assays revealed increased tropism of hGC33-OMVs toward HepG2 cells, while Co-IP confirmed the direct interaction between hGC33 and GPC3. Meanwhile, hGC33-OMVs suppressed HepG2 cell proliferation, induced G1-phase arrest, and reduced Wnt3a, β-catenin, Cyclin D1, and C-myc expression.</p><p><strong>Conclusion: </strong>Engineered <i>E. coli</i> hGC33-OMVs effectively target HCC via the hGC33-GPC3 interaction, inhibit tumor growth by suppressing Wnt signaling, and demonstrate potential for use as a versatile platform for antibody delivery.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6573-6590"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158566","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}