Journal of Drug Delivery Science and Technology最新文献

{"title":"Exploiting the therapeutic efficacy of nanoparticles in the treatment of multidrug-resistant bacteria: Excitements and pitfalls","authors":"Chinyere Aloke ,&nbsp;Chinedu Ogbonnia Egwu ,&nbsp;Olalekan Olugbenga Onisuru ,&nbsp;Sarah Otun ,&nbsp;Ikechukwu Achilonu","doi":"10.1016/j.jddst.2024.106501","DOIUrl":"10.1016/j.jddst.2024.106501","url":null,"abstract":"<div><div>Antimicrobial resistance is a major global threat, as traditional antibiotics are becoming less effective against evolving, resistant microorganisms. To address this challenge, nanoparticles (NPs) are being increasingly exploited as an alternative strategy to combat bacteria. This review examines the use of nanoparticles in managing multi-drug resistant microorganisms, exploring their effectiveness, mechanisms of action, advantages, and disadvantages as microbicidal agents. The study found that nanoparticles can target microbial machinery through various pathways, including disrupting cell membranes, generating reactive oxygen species, altering membrane permeability, among others. However, bacteria have also developed strategies to withstand the effects of NPs, including enzymatic modification of NPs, biofilm formation and adaptation, repulsion through electrostatic interactions. Using nanoparticles as antimicrobial agents offers several advantages, including targeted drug delivery, reduced side effects relative to chemical antimicrobials, decreased likelihood of bacterial resistance, controlled drug release, improved solubility, and lower immunosuppression. However, there are also drawbacks associated with their use, such as nanotoxicity in organs like the lungs, kidneys, and liver, limited characterization techniques, buildup of administered NPs in tissues and organs, among others. Therefore, NPs are efficacious, and it is crucial to understand the process through which NP complexes hinder or eradicate bacteria, considering their potential as therapeutic agents.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106501"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NVP-based molecularly imprinted hydrogel contact lenses for sustained delivery of Naringenin: In vitro, Ex vivo, cytocompatibility, anti-inflammatory and ISO standardized physicochemical evaluation","authors":"Syed Ali Faran ,&nbsp;Joseph Dowling ,&nbsp;Richie Ryan ,&nbsp;Peter McLoughlin ,&nbsp;Laurence Fitzhenry","doi":"10.1016/j.jddst.2024.106511","DOIUrl":"10.1016/j.jddst.2024.106511","url":null,"abstract":"<div><div>Naringenin (NAR), due to poor aqueous solubility, faces hindrances in clinical applications to prevent eye diseases such as age-related macular degeneration (AMD). Herein, molecularly imprinted (MiF) contact lenses were fabricated for sustained NAR release and improved corneal and scleral permeability. NAR-imprinted MiF lenses were manufactured employing injection molding and thermal polymerization approach and were characterised according to ISO standards. Template removal, NAR competitive reloading, <em>in vitro</em> release<em>, ex vivo</em> porcine corneal and scleral permeation and <em>in vitro</em> biocompatibility assays were performed. Fabricated MiF lenses showed 74 − 78 % water content, 1.373 ± 0.002 refractive index, &gt;95 % optical transparency, contact angle of 44.4 ± 0.3° and Young's moduli of 0.69 ± 0.08 MPa. Molecular docking (MD) showed strong interactions between NAR and hydrogel matrix (Biotrue® monomer mixture). NAR loading of 40–50 μg/mg of dry MiF lenses with 3.8–4.2 imprinting factor was measured with significantly greater NAR selectivity (p &lt; 0.05) towards imprinted cavities over quercetin (QCN) − analogous to NAR. MiF lenses showed 50 − 63 % sustained NAR <em>in vitro</em> release over 120 h, followed by <em>ex vivo</em> corneal and scleral accumulation of 6.10 <em>±</em> 1.4 to 14.63 <em>±</em> 1.8 μg/cm², respectively. Immortalized human corneal epithelial cells (IM-HCEpiC) and adult retinal pigment epithelium (ARPE-19) cell-focused cytocompatibility and anti-inflammatory studies demonstrated strong clinical and commercialization potential of developed MiF lenses for ocular applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106511"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of hot melt extruded polycaprolactone (PCL) matrices for an oral ultra-long-lasting delivery of galantamine for Alzheimer's disease therapy","authors":"Vinícius Müller ,&nbsp;Bárbara Sthéfani Caldas ,&nbsp;Eduardo Radovanovic ,&nbsp;Edvani Curti Muniz","doi":"10.1016/j.jddst.2024.106464","DOIUrl":"10.1016/j.jddst.2024.106464","url":null,"abstract":"<div><div>Galantamine Hydrobromide (GAL) is a tertiary alkaloid, acting as a competitive and reversible cholinesterase inhibitor. It is indicated for the symptomatic treatment of patients from mild to moderate dementia level of the Alzheimer's disease (AD) type. For treatment of mild to moderate AD, GAL is generally combined with other drugs. The purpose of this work was development and characterization of hot melt extruded (HME) matrices based on polycaprolactone (PCL) for GAL oral ultra-long-lasting delivery. PCL is a biodegradable polymer, biocompatible, water-insoluble and excellent for HME process. From HME drug and polymer mixtures arms from 1 % up to 50 wt-% of GAL were obtained. The raw materials and the as-obtained HME arms were characterized by particle size distribution (PSD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), wide angle x-ray scattering (WAXS) and dissolution test. Our findings showed that GAL possesses polymorphic crystalline form I. It is thermodynamically stable, and remains its particle size and crystalline form even after HME process. Crystallization temperature of PCL increases with GAL content, indicating strong heterogeneous nucleating effect of drug on polymer crystallization process. SEM morphological analysis indicates continuous polymeric phase on surface. However, higher amounts of GAL (50/50 wt-%) presented clusters and heterogeneity, especially in extruded cross-section. It may have influenced the drug release property, decreasing the sustained release ability, due to the transport of medium molecules through the bulk extrudates by GAL soluble clusters. The diffractograms (WAXS) showed patterns peaks of GAL and PCL, indicating that GAL remains its crystalline structure and PCL recrystallized. In the dissolution test, PCL/GAL 80/20 and 90/10 achieved 100 % drug release over seven days and profiles that can be tuned by varying GAL concentration. Finally, we demonstrate the feasibility of using HME process based on the mixture of PCL and GAL as proposals for oral therapies for conditions of AD. This is the first report showing PCL-GAL polymer matrices that achieves several-days drug release.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106464"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing cancer treatment: ROS-induced apoptosis via nanoformulated alkaloids","authors":"Swathi Putta ,&nbsp;Santhosh Kumar Chinnaiyan ,&nbsp;Ramadevi Korni ,&nbsp;Venkata Radha Gadela","doi":"10.1016/j.jddst.2024.106556","DOIUrl":"10.1016/j.jddst.2024.106556","url":null,"abstract":"<div><div>Cancer is a universal health issue, killing one in every six people across the world. The treatment of cancer is a complicated task, conventional therapies alone and combined therapy also have serious challenges due to cancer cells non-specificity. However, advanced target-based therapies like ablation therapy, stem cell therapy, natural antioxidants, and nanoparticles are emerging to protect against non-cancer cell toxicity. Recently targeted therapies focus on Reactive oxygen species (ROS) induced cytotoxicity. They activate apoptotic signaling molecules using small molecules to target cancer cells. Several plant compounds have reported their anticancer activity via induced apoptosis with ROS mediators in cancer cells. Among plant-derived compounds, alkaloids are widely used in cancer therapy, some of which can mediate ROS by targeting various cellular components such as proliferation, cell cycle, tumor suppression, metastasis, and apoptosis. The effectiveness of alkaloids is limited due to their low solubility, poor bioavailability, and lack of specificity for targeting cancer cells. To overcome this limitation, nanoformulations are the promising approach for effective target drug delivery. Nanocarriers like liposomes, micelles, dendrimers, and nanoparticles are designed to deliver alkaloids effectively to tumor sites, ensuring optimal drug concentrations and overcoming the challenging tumor microenvironment. This review adopts an evidence-based approach to identify and evaluate the nanoformulated alkaloid and the ROS-mediated apoptosis signaling pathway against multiple cancers as a possible therapeutic option.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106556"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143105161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging innovations in nanomedicine for cancer immunotherapy","authors":"Jaimin R. Shah ,&nbsp;Devesh U. Kapoor ,&nbsp;Bhupendra G. Prajapati","doi":"10.1016/j.jddst.2024.106584","DOIUrl":"10.1016/j.jddst.2024.106584","url":null,"abstract":"<div><div>Cancer is characterized by a highly intricate pathophysiology and stands as a chief cause of mortality and illness globally. Traditional treatments for cancer such as chemotherapy, targeted &amp; radiation therapy, and immunotherapy. Despite their widespread use, these therapies have significant limitations. They often suffer from a lack of selectivity, resulting in non-targeted cytotoxic effects that harm healthy tissues. Moreover, these treatments frequently encounter challenges such as inadequate drug delivery to sites of tumor and the development of multi-drug resistance, which collectively diminish their overall effectiveness and potency in combating cancer. Nanoparticles (NPs) are increasingly employed as a nanomedicine platform in cancer immunotherapy, thanks to their exceptional physicochemical characteristics, such as size, shape, and surface attributes. This manuscript explores the challenges posed by the tumor microenvironment (TME) in cancer treatment and presents innovative strategies utilizing nanomaterials-based formulations. The resistance of the TME, particularly its physical and immunosuppressive barriers, impedes the efficacy of conventional therapies. We discuss the pharmacodynamics and pharmacokinetics of nanomaterials within the TME, highlighting their role in modifying cancer-immunity phenotypes. The regulation of the TME is critical, with a focus on modulating tumor blood vessels and extravascular components to enhance therapeutic outcomes. Additionally, the manuscript delves into the potential of nanomaterials-based immunotherapy, which can trigger the tumor-specific antigens release, facilitate their presentation, and prime T cells for effective anti-tumor responses. The integration of nanomaterials-based delivery systems in combination immunotherapy is also explored, showcasing the synergy between nanomedicine and other therapeutic modalities, such as chemotherapy and gene therapy. This comprehensive review underscores the promise of nanomaterials in redefining cancer treatment by overcoming TME-associated resistance and improving immunotherapeutic efficacy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106584"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detachable dissolvable microneedles maintain the viability of phage cocktail and effectively disrupt Pseudomonas aeruginosa biofilm","authors":"Ahmad Efendi ,&nbsp;Ampapan Naknaen ,&nbsp;Supanan Ampawa ,&nbsp;Nichakan Miengmern ,&nbsp;Vorrapon Chaikeeratisak ,&nbsp;Supason Wanichwecharungruang","doi":"10.1016/j.jddst.2024.106527","DOIUrl":"10.1016/j.jddst.2024.106527","url":null,"abstract":"<div><div>The current treatment of <em>Pseudomonas aeruginosa</em> infection remains challenging because of antimicrobial-resistant bacteria. Phage therapy has gained more attention due to its ability to kill specific bacteria without infecting human cells. Nevertheless, phage stability in limited environments and the biofilm shield created by the pathogenic bacteria are the challenges for phage therapy implementation. To tackle the phage stability challenge, we focus on optimizing materials that can stabilize phages in a solid environment. Our research reveals that the combination of hyaluronic acid (HA) and gelatin in the solid state provides better stability for the two representative phages against <em>P. aeruginosa</em>, PhiKZ, and SPAO1, compared to a typical liquid medium. To solve the biofilm problem specifically in skin infection, we made the phage-loaded HA-gelatin into detachable dissolvable microneedles (DDMNs). The mechanical properties of the obtained DDMNs are sufficient to allow them to penetrate fresh <em>ex vivo</em> porcine skin easily. Using <em>P. aeruginosa</em>-inoculated membranes well shielded with biofilm created by the bacteria, our tests revealed that the phage-loaded HA-gelatin microneedles could be deposited in the bacterial-occupied membrane, disrupting the biofilm and killing <em>P. aeruginosa.</em></div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106527"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-cancer and immunomodulatory photodynamic therapy application of novel porphyrin derivatives","authors":"Harika Topal Önal ,&nbsp;Esra Aydemir ,&nbsp;Derya Yetkin ,&nbsp;Özgül Hakli Tutuş ,&nbsp;Furkan Ayaz","doi":"10.1016/j.jddst.2024.106513","DOIUrl":"10.1016/j.jddst.2024.106513","url":null,"abstract":"<div><div>Breast cancer is a common and fatal disease among women, with treatment options including surgery, chemotherapy, radiotherapy, and photodynamic therapy (PDT). PDT uses photosensitizers to destroy malignant cells. In this study, two new asymmetric porphyrin derivatives, POR1 and POR2, were synthesized. One contains a sulfur atom, while the other has a nitrogen atom. The compounds were characterized using spectroscopic methods. The cytotoxic effects of POR1 and POR2 were evaluated on MDA-MB-231 and MCF-7 breast cancer cell lines. Apoptotic data showed that POR1 increased cell death by 62 % in MCF-7 and 58 % in MDA-MB-231 cells, significantly higher than under dark conditions (less than 40 % for both cell lines). The IC₅₀ values for POR1 and POR2 were 7 μg/mL and 8 μg/mL, respectively, indicating strong cytotoxicity in MCF-7 cells at low concentrations. These effects were observed with and without xenon light exposure, suggesting the potential of POR derivatives as effective PDT agents. The selectivity of the compounds was evaluated on 3T3 fibroblast cells, showing lower cytotoxicity in healthy cells, indicating cancer cell selectivity, especially under light activation. Additionally, the effects of POR1 and POR2 on TNF-α and IL-6 production were studied in Raw 264.7 macrophages to explore their immunomodulatory potential. The Notch1 signaling pathway, relevant to breast cancer and immune response, was also assessed. Our findings suggest that POR1 and POR2 are promising PDT agents with anti-inflammatory and immunomodulatory properties, making them strong candidates for cancer therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106513"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143100569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal delivery of transferrin conjugated chitosan nanoparticles to the brain: A comparative analysis of conjugated and un-conjugated nanoparticles in vivo","authors":"Annu ,&nbsp;Ali Sartaj ,&nbsp;Zufika Qamar ,&nbsp;Eman Aldosari ,&nbsp;Sanjula Baboota ,&nbsp;Javed Ali","doi":"10.1016/j.jddst.2024.106550","DOIUrl":"10.1016/j.jddst.2024.106550","url":null,"abstract":"<div><h3>Background</h3><div>The current research aims to design transferrin (Tf) conjugated chitosan (CH) nanoparticles (NPs) of lurasidone hydrochloride (LH) for schizophrenia.</div></div><div><h3>Methods</h3><div>Ionic gelation technique was adopted to produce CH-NPs followed by Tf-thiolation. Designed NPs were assessed for <em>in vitro</em> drug release and <em>in vivo</em> pharmacokinetics studies to assess their brain-targeting efficiency. The efficacy and safety of designed NPs were evaluated in ketamine-induced Wistar rats.</div></div><div><h3>Results</h3><div><em>In vitro</em> drug release revealed supremacy of optimized NPs over LH-suspension owing to higher and sustained release of LH. A remarkable growth in drug concentration to the brain was discerned from designed NPs in comparison to LH-solution after intranasal administration (IN). A, marked increment in the antipsychotic potential of LH from NPs with enhanced anti-inflammatory and neuroprotective potential in comparison to LH-solution was observed.</div></div><div><h3>Conclusion</h3><div><em>In vivo,</em> results established the primacy of optimized NPs in inflating the brain delivery and therapeutic prospect of LH.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106550"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143105105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers in therapeutic interventions for epilepsy: Nanocarriers as a pivotal catalyst in the synergistic combination of conventional antiepileptics and herbal drugs","authors":"Ajay Pratap Singh Chauhan,&nbsp;Devika Unnithan,&nbsp;Rabnoor Alam,&nbsp;Harshita Singh,&nbsp;Rabea Parveen,&nbsp;Azka Gull,&nbsp;Saba Khan,&nbsp;Javed Ali","doi":"10.1016/j.jddst.2024.106547","DOIUrl":"10.1016/j.jddst.2024.106547","url":null,"abstract":"<div><div>Epilepsy, a prevalent and frequently incapacitating neurological disease affecting over 50 million people worldwide, exhibits substantial treatment challenges, particularly in one-third of patients who are resistant to traditional antiepileptic drugs (AEDs). This review explores combinational approaches to enhance epilepsy therapy by combining AEDs with herbal medicines and utilizing nanotechnology to improve drug delivery. Combining drugs within a single nanoformulations, such as liposomes, polymeric nanoparticles, nanoemulsions, nanocrystals, nanostructured lipid carriers, smart thermosetting hydrogels and spanlastics which have the potential to enhance drug targeting, prolong release, and minimize adverse effects. This article talks about the advantageous pharmacokinetic and pharmacodynamic characteristics of nanoformulations from multiple studies including how they can effectively target the brain. It also provides several examples of notable advancements in utilizing nanotechnology for epilepsy treatment. Furthermore, it explores the complex pathways that contribute to drug resistance in epilepsy, highlighting the insistent challenges in attaining effective therapy. Nanocarrier-based delivery systems are proposed as a plausible way to overcome the blood-brain barrier and other biological challenges, providing enhanced pharmacokinetic and pharmacodynamic properties. Although polypharmacy has historically been employed for drug-resistant epilepsy, the absence of thorough clinical studies highlights the pressing necessity for rigorous research to validate these approaches. Conclusively, the review proposes a comprehensive approach that combines AEDs with herbal drugs using novel nanocarriers to boost the effectiveness of treatment and the results for patients with Drug-resistant epilepsy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106547"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143105168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-delivery of JQ1 and Gambogic acid through tumor-targeting PEGylated nanographene oxide with FSH beta peptide (33–53) identifies SNHG7-hsa-miR-324-3p-SMAD2 axis as a prognostic biomarker in ovarian cancer","authors":"Boddapati Kalyani Bhardwaj,&nbsp;Sanu Thankachan,&nbsp;Padmanaban S. Suresh","doi":"10.1016/j.jddst.2024.106537","DOIUrl":"10.1016/j.jddst.2024.106537","url":null,"abstract":"<div><div>Gynecological malignancies including ovarian cancer have high mortality rates. The present work investigates if pGO-FSH-JQ1-Gambogic acid (GA) nanoparticles can target FSH-overexpressing ovarian cancer cells. The synergistic anti-ovarian cancer activity of JQ1, a bromodomain inhibitor, and Gambogic acid, were tested and assessed for cell proliferation, apoptosis, anti-angiogenic properties, and gene expression modulation. MTT, in ovo-CAM, annexin V-/PI, and live/dead cell assays using AO/ETBR staining showed that pGO-FSH-GA-JQ1 nanoparticles caused dose-dependent cell death and apoptosis, in Caov-3 cells after 48 h. Additionally, the FSH β 33–53 peptide specifically targeted FSHR in ovarian cancer cells, resulting in enhanced apoptosis. Whole transcriptome sequencing showed significantly downregulated gene expression of several critical genes implicated in ovarian cancer progression, including SMAD2. Quantitative real-time PCR confirmed that the pGO-FSH-GA-JQ1 nanoparticles altered gene expression of TGFβ pathway genes (SMAD2, SMAD4, TGFBRII, and SIN3A), associated genes (CTNNB1 and FOS), angiogenesis marker (VEGFB), cell proliferation marker (CDK6), and EMT regulating marker (CCNG2). A novel axis, SNHG7/hsa-miR-324–3p/SMAD2, targeted by JQ1 and GA, was also found using whole transcriptome sequencing and bioinformatics analysis. This novel axis may be a predictive factor for ovarian cancer treatment efficacy. Experimental results suggest that pGO-FSH-JQ1-GA nanoparticles may be an effective and synergistic ovarian cancer-targeted therapy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"104 ","pages":"Article 106537"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143105186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}