Journal of Drug Targeting最新文献

{"title":"A novel mucoadhesive phytic acid grafted chitosan nanocarrier encapsulated with cisplatin for site-specific cervical cancer therapy: <i>in vitro</i> and <i>in vivo</i> assessments.","authors":"Ivy Saha, Jitu Halder, Tushar Kanti Rajwar, Vineet Kumar Rai, Deepak Pradhan, Ajit Mishra, Ritu Mahanty, Priyanka Dash, Chandan Das, Bibhanwita Satpathy, Salim Manoharadas, Subramanian Palanisamy, Saurjit Mohapatra, Biswakanth Kar, Goutam Ghosh, Goutam Rath","doi":"10.1080/1061186X.2025.2519599","DOIUrl":"10.1080/1061186X.2025.2519599","url":null,"abstract":"<p><p>A mucoadhesive vaginal drug delivery system offers a promising strategy to mitigate chemotherapy-associated systemic toxicity in cervical cancer (CC). Metalloenzymes like superoxide dismutase 2 (SOD2) and catalase are responsible for maintaining oxidant-antioxidant balance in cancer cells. The present study proposed a new approach to prepare cisplatin-loaded phytic acid crosslinked chitosan nanoparticles (CisPANP). CisPANP exhibited a particle size (PS) of 278.24 ± 15.64 nm with a zeta potential of +39 ± 2.46 mV. The nanoparticles demonstrated a sustained drug release behaviour, i.e. 86.85 ± 6.38% drug was released in 24 h. CisPANP were observed to significantly downregulate the expression of SOD and catalase by 3.5 and 1.7-fold, respectively, as compared to untreated cells. CisPANP further increased ROS level and inhibited HeLa cell viability. The <i>in vivo</i> anti-cancer efficacy of CisPANP was evaluated in EAC cell line-induced CC mice model. The tumour volume in CisPANP was significantly reduced as compared to pure cisplatin (pure Cis). CisPANP was well-retained making Cis available in the vagina. From the histopathology, significant adverse effects were not observed in the surrounding tissue of tumour treated with CisPANP, indicating its safety. From the observations of the present investigation, CisPANP could serve as a potential candidate for the localised treatment of CC.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-17"},"PeriodicalIF":4.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing chemotherapy for colorectal cancer: EGFR-conjugated ferritin nanocages for targeted doxorubicin delivery.","authors":"Fatemeh Zali, Mohammad Ahmadi, Mohammad Ahmadyousefi, Alisa Khodadadi Kohlan, Neda Alizadeh, Meysam Soleimani","doi":"10.1080/1061186X.2025.2517648","DOIUrl":"10.1080/1061186X.2025.2517648","url":null,"abstract":"<p><p>Biomimetic nanoparticles, exemplified by ferritin, have emerged as a novel approach in drug delivery systems, designed to improve both the biocompatibility of drugs and their targeting. The clinical application of doxorubicin (Dox) is impeded by systemic toxicity and multidrug resistance, emphasising the necessity for innovative delivery platforms. In this research, we proposed the hypothesis that a protein-based nanocage, decorated with an anti-epidermal growth factor receptor (EGFR) peptide as a targeting ligand on its surface, has the potential to enhance the targeted delivery of Dox while reducing systemic toxicity. <i>In vitro</i> studies with the CT26 murine colorectal cancer (CRC) cell line demonstrate marked toxicity and suppression of cell migration, indicating the potential of these nanocages to inhibit metastasis. <i>In vivo</i> experiments using established tumour-bearing mice further confirm the therapeutic efficacy of these nanocages, showing a significant reduction in tumour growth, prolonged survival and diminished systemic toxicity compared to free Dox. In addition, cytokine analysis underscored the immunomodulatory capabilities of M1-linker-QRH in the context of cancer treatment. By addressing critical challenges in drug delivery, this platform holds promise for advancing precision oncology and improving clinical outcomes for patients with CRC.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-11"},"PeriodicalIF":4.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous GABA as a natural epigenetic modifier for managing glycemic memory and diabetic nephropathy by modifying the epigenetic axis.","authors":"Kriti Kushwaha, Debojyoti Mandal, Sourbh Suren Garg, Rupal Dubey, Navneet Khurana, Jeena Gupta","doi":"10.1080/1061186X.2025.2523990","DOIUrl":"10.1080/1061186X.2025.2523990","url":null,"abstract":"<p><strong>Background: </strong>Glycemic memory plays a crucial role in the progression of diabetic nephropathy (DN), even after glycemic control is achieved. This study aimed to evaluate γ-aminobutyric acid (GABA), a natural compound identified to be 82.5% structurally similar to metformin, for its potential in mitigating glycemic memory and DN.</p><p><strong>Methods: </strong>A structural similarity search identified GABA as a potential analog of metformin. Molecular docking was conducted with the SIRT1 protein, and ADME profiling was performed. In vitro assays evaluated antioxidant activity (DPPH assay), cytotoxicity (MTT assay), oxidative stress biomarkers, and histone acetylation. In vivo experiments were conducted in high-fat diet-fed Sprague-Dawley rats subjected to dietary reversal and GABA treatment to assess the effects on glycemic control, lipid metabolism, renal and hepatic function, oxidative stress, and epigenetic modulation.</p><p><strong>Results: </strong>GABA exhibited strong binding affinity to SIRT1 (-5.8 kcal/mol) and favorable ADME characteristics. It demonstrated potent antioxidant activity (DPPH IC₅₀: 141.09 µg/mL) and high cell viability (90.82% at 5 µM), with no cytotoxicity up to 150 µM. In vitro, GABA reduced oxidative markers and restored histone H3 acetylation. In in vivo, DR GABA (200mg/kg) significantly improved lipid profiles: Cholesterol was reduced by 44.44%, Triglycerides by 28.64%, and LDL by 40.80%. Conversely, HDL increased by 103.65%. Kidney function (100mg/kg DR GABA) showed a reduction in blood urea by 30.43%, Creatinine by 4.65%, and Uric acid by 75.00%. Liver function tests (100mg/kg DR GABA) significantly lowered Bilirubin by 53.57%, SGOT/AST by 54.24%, SGPT/ALT by 39.52%, and Alkaline Phosphatase by 60.58% as compared to the control group, and histopathological features indicated reduced inflammation and improved glomerular structure.</p><p><strong>Conclusion: </strong>GABA, a metformin analog, exhibits antioxidant, renoprotective, and hepatoprotective properties. By improving metabolic profiles and restoring epigenetic regulation, GABA shows promise as a novel therapeutic agent for addressing glycemic memory and preventing the progression of diabetic nephropathy.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-21"},"PeriodicalIF":4.3,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Efficacy of pDNA Vaccine Candidate Against SARS-CoV-2 in Syrian Golden Hamsters.","authors":"Iman Almansour Alzamil, Serguei Golovan, Jennifer Pickens, Krista Salley, Michael Roberts","doi":"10.1080/1061186X.2025.2521811","DOIUrl":"10.1080/1061186X.2025.2521811","url":null,"abstract":"<p><p>Seasonal SARS-CoV-2 vaccination is known as an efficient way to control the COVID-19 pandemic. However, the currently approved mRNA and protein vaccines are thermally unstable and require further encapsulation and ultra-cold chain transportation and storage. Therefore, alternative platforms that can overcome this limitation are needed. pDNA has emerged as an attractive next-generation vaccine platform due to its high thermal stability. Here, we developed pDNA-based SARS-CoV-2 vaccine candidate and conducted a preclinical evaluation in Syrian golden hamsters. We assessed the immunogenicity of the vaccine candidate as measured by S-specific immune responses ad well as neutralization. Administration of S.opt.FL pDNA vaccine induced was able to induce higher S-specific SARS-CoV-2 binding and neutralizing antibody levels. Importantly, S-specific IgG2 which represented Th1-mediated immune responses was predominantly induced after pDNA vaccination. Besides, animal group receiving three doses induced higher neutralizing antibody responses compared to animal group receiving two doses. In addition, we evaluated the protective efficacy of the pDNA vaccine. We determined that the Th1-skewed immune response was important in conferring protection upon virus challenge. These results indicates that intramuscular delivery of S.opt.FL pDNA vaccine is safe and effective in preventing SARS-CoV-2 infection. In addition, the study shed new light on the importance of the IgG isotype for the development of SARS-CoV-2 vaccine candidates. Furthermore, our findings can be used to support further testing of several pDNA-based vaccine candidates against other pathogens.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/1061186X.2025.2522497","DOIUrl":"https://doi.org/10.1080/1061186X.2025.2522497","url":null,"abstract":"","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1"},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in targeted therapy for triple-negative breast cancer: a review of key antigens and recent advances.","authors":"Bahman Akbari, Md Mehedi Hasan, Shahidul M Islam","doi":"10.1080/1061186X.2025.2520306","DOIUrl":"10.1080/1061186X.2025.2520306","url":null,"abstract":"<p><p>The most aggressive subtype of breast cancer is triple-negative breast cancer (TNBC), which affects about 10-15% of all breast cancer cases. TNBC is associated with a poor prognosis and drug resistance due to the lack of oestrogen, progesterone, and HER2 receptors. Developing targeted immunotherapy for TNBC was challenged by identifying TNBC-specific antigens that can be suitable targets for antibody and nanobody-based therapies. Evidence from cancer- targeted therapy demonstrates that treatment outcomes are more successful when the target antigen is either overexpressed in tumour tissue or exhibits tumour specificity. Several antigens have been overexpressed in TNBC, including programmed cell death protein 1 (PD-1), programmed death-ligand 1(PD-L1), mesothelin (MSLN), trophoblast cell-surface antigen 2 (Trop-2), tumour endothelial marker 8 (TEM8), etc. There have been investigations targeting these antigens with antibodies, nanobodies, small molecules, peptides, and miniproteins for targeted treatment of TNBC. Antibodies known as Aembrolizumab, Atezolizumab, and Sacituzumab Govitecan-hziy have been approved by the FDA, and many are under investigation. The present review discusses the antigens with high expression in TNBC, their role in cancer development and progression, and the targeted therapies like antibodies, recombinant proteins, and antibody-drug conjugates (ADC).</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-20"},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered <i>Salmonella</i> carrying siRNA-PD-1 shrinks orthotopically implanted bladder cancer in rats.","authors":"Qizhong Shi, Jiaxin Geng, Lulu Han, Xingchan Ji, Jiaoran Li, Yonghui Mu, Tiesuo Zhao, Lei Wang, Huijie Jia","doi":"10.1080/1061186X.2025.2512619","DOIUrl":"10.1080/1061186X.2025.2512619","url":null,"abstract":"<p><strong>Background: </strong>Currently, the application of engineered bacteria in tumour treatment has received increasing attention. It has been proved that Bacillus Calmette-Guerin (BCG) can effectively treat bladder cancer (BC). In addition, immune checkpoint blockade is an effective method for tumour treatment. Programmed cell death protein 1 (PD-1), an important immunosuppressive molecule, binds to programmed death ligand receptor 1 (PD-L1) and inhibits the anti-tumour effects of T cells.</p><p><strong>Methods: </strong>The plasmid encoding siRNA-PD-1 was constructed, and the rat BC <i>in situ</i> model was established. After the treatment, morphological changes in tumour tissue were detected by HE staining, and the apoptotic cells in tumour tissue were detected by TUNEL. The expression of related proteins was detected by Western blotting, and the proportion of CD4⁺ and CD8⁺ T cells in the spleen was detected by flow cytometry.</p><p><strong>Results: </strong>We found that the engineered <i>Salmonella</i> significantly inhibited the growth and incidence of tumours and increased the apoptosis of tumours. Importantly, engineered <i>Salmonella</i> carrying siRNA-PD-1 enhanced the anti-tumour immune response by inhibiting PD-1 expression and increased the CD8⁺ T cell infiltration in tumour tissue, while elevating the ratio of CD8⁺/CD4⁺ in spleens.</p><p><strong>Conclusion: </strong>We demonstrated that engineered <i>Salmonella</i> siRNA-PD-1 exerted significant anti-tumour effects on BC.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-9"},"PeriodicalIF":4.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiopep-2 modified naringin nanoparticles for Alzheimer's disease therapy overcoming BBB.","authors":"Jing Jiang, Yue Xing, Shumeng Liu, Yue Na, Xia Lei, Fang Geng, Yafeng Zhang, Lihong Yang, Ning Zhang","doi":"10.1080/1061186X.2025.2514575","DOIUrl":"10.1080/1061186X.2025.2514575","url":null,"abstract":"<p><p>Naringin (4',5,7-trihydroxyflavanone-7-rhamnoglucoside, NG), a potential treatment for Alzheimer's disease (AD), has strong neuroprotective effects but is limited by poor solubility, low bioavailability, and limited brain accumulation. To address these issues, we developed ANG-NG-NPs, a novel NG-loaded poly (ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) nanoparticle modified with the brain-targeting peptide Angiopep-2 (TFFYGGSRGKRNNFKTEEY, ANG). ANG-NG-NPs exhibited an average size of 126.1 ± 4.50 nm, a zeta potential of -2.97 ± 0.29 mV, 73.43 ± 0.80% encapsulation efficiency (EE), and 24.68 ± 0.45% drug loading capacity (LC). <i>In vitro</i> release studies confirmed its sustained-release properties. <i>In vivo</i>, ANG-NG-NPs extended NG's circulation time and increased brain uptake. Notably, ANG-NG-NPs restored learning and memory in APP/PS1 mice, improved hippocampal cell health, and reduced hyperphosphorylated tau protein (p-Tau) expression. These findings suggest ANG-NG-NPs as a promising brain-targeting system for treating central nervous system disorders.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold nanoparticles: diagnostic and therapeutic applications in neurodegenerative disorders.","authors":"Xin Hu, Jingxian Cheng, Ruri Yuan, Yiting Zhou, Jiajia Rao, Ying Wan, Yi Li, Xiao Zhang, Rong Li","doi":"10.1080/1061186X.2025.2509287","DOIUrl":"10.1080/1061186X.2025.2509287","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases, pose a significant and escalating health challenge in the context of an ageing population. Gold nanoparticles (GNPs) have emerged as promising agents in the diagnostic and therapeutic realms of NDDs, due to their unique ability to enhance drug delivery across the blood-brain barrier (BBB). This paper presents a comprehensive review of the application of GNPs in the context of NDDs diagnosis and therapy, highlighting their potential to transform patient management. Additionally, we systematically address the critical challenges associated with the use of GNPs in the treatment and diagnosis of NDDs, focusing on pharmacokinetics and metabolism, toxicity, long-term biocompatibility, regulatory challenges and cost-effectiveness. Furthermore, we synthesise ongoing clinical studies to provide a holistic perspective on the current state of research in this field. We also explore the prospective trajectories and clinical translational potential of GNPs, which may usher in a new era in the treatment of NDDs.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-18"},"PeriodicalIF":4.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of treating ulcerative colitis and colon cancer by using oral colon targeted drug delivery system based on polymer micelles.","authors":"Shuangshuang Li, Te Li, Xueni Wang, Aysha Rahmatulla, Yuefeng Zhao, Xinran Zhang, Yuxuan Liu, Yuzhou Chen","doi":"10.1080/1061186X.2025.2514564","DOIUrl":"10.1080/1061186X.2025.2514564","url":null,"abstract":"<p><p>Ulcerative colitis (UC) and colon cancer (CC) represent significant global health burdens. Current first-line chemotherapeutic agents, including capecitabine, oxaliplatin and irinotecan, face two principal limitations: poor tumour specificity and dose-limiting toxicities. The oral colon targeted drug delivery system (OCTDDS) has garnered significant research interest for its capacity to enhance therapeutic outcomes in colonic pathologies. Polymeric micelles, self-assembled nanostructures formed by amphiphilic block copolymers, have emerged as promising OCTDDS platforms. These nanocarriers enhance the bioavailability of hydrophobic agents, preserve pharmaceutical integrity in gastrointestinal transit, facilitate tumour-specific cellular internalisation, and enable spatiotemporal drug release profiles, collectively optimising therapeutic efficacy. Based on explaining the pathological mechanisms of colonic diseases, this review describes the traditional OCTDDS targeting strategy, reviews the targeting approaches of polymer micelles in treating UC and CC, summarises common hydrophilic and hydrophobic groups, as well as copolymers used in polymer micelles, discusses the preparation methods and characterisation techniques of polymer micelles, and examines research studies on oral colon-targeted polymer micelles. This review aims to provide a reference for the further design and development of OCTDDSs using polymer micelles as carriers.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-26"},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}