Journal of Drug Targeting最新文献_第4页

Integrating machine learning and multitargeted drug design to combat antimicrobial resistance: a systematic review. 整合机器学习和多靶点药物设计以对抗抗菌药耐药性：系统综述。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-03-01 Epub Date: 2024-11-26 DOI: 10.1080/1061186X.2024.2428984

Nagmi Bano, Salman Arafath Mohammed, Khalid Raza

{"title":"Integrating machine learning and multitargeted drug design to combat antimicrobial resistance: a systematic review.","authors":"Nagmi Bano, Salman Arafath Mohammed, Khalid Raza","doi":"10.1080/1061186X.2024.2428984","DOIUrl":"10.1080/1061186X.2024.2428984","url":null,"abstract":"Antimicrobial resistance (AMR) is a critical global health challenge, undermining the efficacy of antimicrobial drugs against microorganisms like bacteria, fungi and viruses. Multidrug resistance (MDR) arises when microorganisms become resistant to multiple antimicrobial agents. The World Health Organisation classifies AMR bacteria into priority list - I (critical), II (high) and III (medium), prompting action from nearly 170 countries. Six priority bacterial strains account for over 70% of AMR-related fatalities, contributing to more than 1.3 million direct deaths annually and linked to over 5 million deaths globally. Enterobacteriaceae, including Escherichia coli, Salmonella enterica and Klebsiella pneumoniae, significantly contribute to AMR fatalities. This systematic literature review explores how machine learning (ML) and multitargeted drug design (MTDD) can combat AMR in Enterobacteriaceae. We followed PRISMA guidelines and comprehensively analysed current prospects and limitations by mining PubMed and Scopus literature databases. Innovative strategies integrating AI algorithms with advanced computational techniques allow for the analysis of vast datasets, identification of novel drug targets, prediction of resistance mechanisms, and optimisation of drug molecules to overcome resistance. Leveraging ML and MTDD is crucial for both advancing our fight against AMR in Enterobacteriaceae, and developing combination therapies that target multiple bacterial survival pathways, reducing the risk of resistance development.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"384-396"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621808","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}

引用次数: 0

Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing. 克服抗生素耐药性：药物再利用的潜力与陷阱。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-03-01 Epub Date: 2024-11-12 DOI: 10.1080/1061186X.2024.2424895

Mohammad Abavisani, Alireza Khoshrou, Souzan Eshaghian, Sercan Karav, Amirhossein Sahebkar

{"title":"Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing.","authors":"Mohammad Abavisani, Alireza Khoshrou, Souzan Eshaghian, Sercan Karav, Amirhossein Sahebkar","doi":"10.1080/1061186X.2024.2424895","DOIUrl":"10.1080/1061186X.2024.2424895","url":null,"abstract":"Since its emergence shortly after the discovery of penicillin, antibiotic resistance has escalated dramatically, posing a significant health threat and economic burden. Drug repositioning, or drug repurposing, involves identifying new therapeutic applications for existing drugs, utilising their established safety profiles and pharmacological data to swiftly provide effective treatments against resistant pathogens. Several drugs, including otilonium bromide, penfluridol, eltrombopag, ibuprofen, and ceritinib, have demonstrated potent antibacterial activity against multidrug-resistant (MDR) bacteria. These drugs can disrupt biofilms, damage bacterial membranes, and inhibit bacterial growth. The combination of repurposed drugs with conventional antibiotics can reduce the required dosage of individual drugs, mitigate side effects, and delay the development of resistance, making it a promising strategy against MDR bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Despite its promise, drug repurposing faces challenges such as potential off-target effects, toxicity, and regulatory and intellectual property issues, necessitating rigorous evaluations and strategic solutions. This article aims to explore the potential of drug repurposing as a strategy to combat antibiotic resistance, examining its benefits, challenges, and future prospects. We address the legal, economic, and practical challenges associated with repurposing existing drugs, highlight successful examples, and propose solutions to enhance the efficacy and viability of this approach in combating MDR bacterial infections.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"341-367"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558005","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}

引用次数: 0

siRNA targeting PARP-1 alleviates diabetic peripheral neuropathy in a streptozotocin-induced rat model. 靶向 PARP-1 的 siRNA 可缓解链脲佐菌素诱导的大鼠模型中的糖尿病周围神经病变

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-03-01 Epub Date: 2024-12-16 DOI: 10.1080/1061186X.2024.2431316

Moqbel Ali Moqbel Redhwan, Hariprasad M G, Suman Samaddar, Duaa Bafail, Sumaia Abdulbari Ahmed Ali Hard, Sourav Guha, Apurwa Dhavale

{"title":"siRNA targeting PARP-1 alleviates diabetic peripheral neuropathy in a streptozotocin-induced rat model.","authors":"Moqbel Ali Moqbel Redhwan, Hariprasad M G, Suman Samaddar, Duaa Bafail, Sumaia Abdulbari Ahmed Ali Hard, Sourav Guha, Apurwa Dhavale","doi":"10.1080/1061186X.2024.2431316","DOIUrl":"10.1080/1061186X.2024.2431316","url":null,"abstract":"Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, affecting nearly 50% of diabetic patients and leading to chronic pain, numbness and progressive sensory and motor function loss. This study investigates the potential of siRNA-mediated silencing of poly(ADP-ribose) polymerase 1 (PARP1) to alleviate DPN in a rat model. PARP1 overactivation, driven by hyperglycaemia-induced oxidative stress, exacerbates neuronal damage in DPN. Using chitosan nanoparticles (ChNPs) to deliver PARP1-targeting siRNA intrathecally in diabetic rats induced with streptozotocin (STZ) 55 mg/kg intraperitoneally, we conducted behavioural and physiological assessments, including Sciatic Functional Index (SFI), motor nerve conduction velocity (MNCV), grip strength and pain sensitivity tests, alongside qRT-PCR analyses, to evaluate therapeutic outcomes. Our findings indicate statistically significant improvements, with siRNA ChNPs-mediated PARP1 silencing alleviating neuropathic symptoms in DPN rats (p < .001 for SFI and MNCV improvements). Biochemical analyses revealed reductions in oxidative stress markers, such as MDA, and increased antioxidant levels, including GSH, CAT and SOD (p < .001). Pro-inflammatory cytokines and apoptotic markers, including NF-κB, IL6, IL1β, TNFa, TGF-β, CAS3, CAS9, BAK and BAX, also showed significant reductions (p < .01), confirming the neuroprotective effects of PARP1 inhibition. These results highlight the potential of siRNA-based therapies targeting PARP1 as a promising therapeutic approach for DPN, paving the way for future research with clinical applications.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"424-435"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675065","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}

引用次数: 0

Drug screening approaches for small-molecule compounds in cancer-targeted therapy. 癌症靶向治疗中的小分子化合物药物筛选方法。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-03-01 Epub Date: 2024-11-22 DOI: 10.1080/1061186X.2024.2427185

Yelin Zhao, Chenyu Yuan, Yuchen Shi, Xiaohong Liu, Liaoxin Luo, Li Zhang, Milica Pešić, Hongjuan Yao, Liang Li

引用次数: 0

Reversal potentials of Tween 20 in ABC transporter-mediated multidrug-resistant cancer and treatment-resistant depression through interacting with both drug-binding and ATP-binding areas on MDR proteins. 吐温 20 通过与 MDR 蛋白上的药物结合区和 ATP 结合区相互作用，逆转 ABC 转运体介导的多药耐药性癌症和耐药性抑郁症的潜能。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-03-01 Epub Date: 2024-11-18 DOI: 10.1080/1061186X.2024.2429006

Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng

{"title":"Reversal potentials of Tween 20 in ABC transporter-mediated multidrug-resistant cancer and treatment-resistant depression through interacting with both drug-binding and ATP-binding areas on MDR proteins.","authors":"Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng","doi":"10.1080/1061186X.2024.2429006","DOIUrl":"10.1080/1061186X.2024.2429006","url":null,"abstract":"Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters in vitro and to evaluate its potential for overcoming drug resistance in two models: an in vitro cancer MDR model and an in vivo TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the in vivo depression-like behaviour model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both in vitro and in vivo, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"410-423"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621810","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}

引用次数: 0

Development and optimization of curcumin-loaded solid lipid nanoparticles using Box-Behnken design and evaluation of its efficacy in modulating morphine-induced conditioned place preference: in vivo and in silico studies.

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-02-24 DOI: 10.1080/1061186X.2025.2468758

Amirhossein Babaei, Hossein Ebrahimi, Tina Shokouhi Kouchaksaraei, Seyyed Mohammad Hamidi, Mohadeseh Khazaeialiabad, Ali Siahposht-Khachaki, Pedram Ebrahimnejad

{"title":"Development and optimization of curcumin-loaded solid lipid nanoparticles using Box-Behnken design and evaluation of its efficacy in modulating morphine-induced conditioned place preference: in vivo and in silico studies.","authors":"Amirhossein Babaei, Hossein Ebrahimi, Tina Shokouhi Kouchaksaraei, Seyyed Mohammad Hamidi, Mohadeseh Khazaeialiabad, Ali Siahposht-Khachaki, Pedram Ebrahimnejad","doi":"10.1080/1061186X.2025.2468758","DOIUrl":"10.1080/1061186X.2025.2468758","url":null,"abstract":"Drug addiction, particularly to opioids like morphine, remains a pressing global health issue. Curcumin, a natural flavonoid, holds promise for treating neurological disorders, yet faces challenges, such as poor solubility and limited bioavailability across the blood-brain barrier. Solid lipid nanoparticles offer a solution, facilitating drug delivery to the brain. Using the Box-Behnken design, nanoparticles were optimised, yielding particles sized 152 nm, with a polydispersity index of 0.254, and an encapsulation efficiency of 70.74%. These nanoparticles enhance curcumin concentration and retention in brain tissue. Behavioural experiments using the conditioned place preference (CPP) test confirmed curcumin's impact on morphine addiction and its modulation of c-Fos gene expression. Pharmacological network analysis identified potential mechanisms of action, highlighting common targets in calcium and serotonin pathways. Docking simulations showed curcumin's affinity for proteins like 5HT1A, MAO-A, and TRPV1, relevant to addiction pathways. This research underscores the potential of curcumin-loaded solid lipid nanoparticles as a therapeutic approach for combating opioid addiction and neurological disorders.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-22"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441115","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}

引用次数: 0

Local delivery of ibrutinib by folate receptor-mediated targeting PLGA-PEG nanoparticles to glioblastoma multiform: in vitro and in vivo studies.

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-02-24 DOI: 10.1080/1061186X.2025.2468749

Bahar Morshedi, Mehdi Esfandyari-Manesh, Fatemeh Atyabi, Mohammad Hossein Ghahremani, Rassoul Dinarvand

{"title":"Local delivery of ibrutinib by folate receptor-mediated targeting PLGA-PEG nanoparticles to glioblastoma multiform: in vitro and in vivo studies.","authors":"Bahar Morshedi, Mehdi Esfandyari-Manesh, Fatemeh Atyabi, Mohammad Hossein Ghahremani, Rassoul Dinarvand","doi":"10.1080/1061186X.2025.2468749","DOIUrl":"10.1080/1061186X.2025.2468749","url":null,"abstract":"Glioblastoma multiforme (GBM) is a widespread and life-threatening kind of brain cancer, which has a high mortality rate. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, irreversibly adheres to a conserved cysteine residue of two enzymes BTK and BMX, inhibiting their kinase activities, which leads to suppression of the growth of glioma cells. This study synthesised PLGA-PEG-folate (PPF) polymer and subsequently encapsulated ibrutinib within PPF nanoparticles (IBT-PPF-NPs). H NMR spectra confirmed the synthesis of PPF polymer. The efficiency of IBT-PPF-NPs was 97 ± 2.26% with 8.8 ± 0.2% drug loading. The particle size was 208 ± 4.8 nm. The IC50 value of free ibrutinib, IB-PPF-NPs and ibrutinib encapsulated in PLGA NPs (IB-P-NPs) was 10.2, 7.6 and 10.13 µM in C6 cell lines, whereas in U-87 MG cells was 24.4, 16 and 25.2 µM, respectively. The cellular uptake of FITC-PPF-NPs increased from 47.6% to 90.3% in C6 cells and from 55% to 97.3% in U-87 MG cells compared to FITC-P-NPs. The in vivo results indicate a significant reduction in tumour size in treatment groups in comparison to control groups, while the group that received the intratumoural injection of IB-PPF-NPs exhibited a greater reduction. The folate-targeting agent enhances the nanoparticles' effectiveness by promoting their uptake through the endocytosis pathway.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-16"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441117","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}

引用次数: 0

Preparation, in vitro and in vivo evaluation of phloretin-loaded TPGS/Pluronic F68 modified mixed micelles with enhanced bioavailability and anti-aging activity.

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-02-23 DOI: 10.1080/1061186X.2025.2469753

Jiaying Li, Tingyuan Li, Mingjie Gong, Xiaowen Wang, Qinyang Hua, Xia Jiang, Qilong Wang, Elmurat Toreniyazov, Jiangnan Yu, Xia Cao, Michael Adu-Frimpong, Ximing Xu

{"title":"Preparation, in vitro and in vivo evaluation of phloretin-loaded TPGS/Pluronic F68 modified mixed micelles with enhanced bioavailability and anti-aging activity.","authors":"Jiaying Li, Tingyuan Li, Mingjie Gong, Xiaowen Wang, Qinyang Hua, Xia Jiang, Qilong Wang, Elmurat Toreniyazov, Jiangnan Yu, Xia Cao, Michael Adu-Frimpong, Ximing Xu","doi":"10.1080/1061186X.2025.2469753","DOIUrl":"https://doi.org/10.1080/1061186X.2025.2469753","url":null,"abstract":"Phloretin exhibits strong antioxidant and anti-aging properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterization revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-aging drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-aging effects of phloretin for broader clinical applications.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-45"},"PeriodicalIF":4.3,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483331","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}

引用次数: 0

Development of linagliptin-loaded liposomes using aspartic acid conjugate for bone-targeted delivery to combat osteoporosis.

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-02-21 DOI: 10.1080/1061186X.2025.2467089

Nikita Nirwan, Yakkala Prasanna Anjaneyulu, Yasmin Sultana, Divya Vohora

{"title":"Development of linagliptin-loaded liposomes using aspartic acid conjugate for bone-targeted delivery to combat osteoporosis.","authors":"Nikita Nirwan, Yakkala Prasanna Anjaneyulu, Yasmin Sultana, Divya Vohora","doi":"10.1080/1061186X.2025.2467089","DOIUrl":"10.1080/1061186X.2025.2467089","url":null,"abstract":"Osteoporosis is a common metabolic bone disorder that requires new treatment strategies. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a proven osteogenic agent in diabetes-linked bone loss. However, poor solubility, low oral bioavailability and inadequate bone-targeting limit its use in osteoporosis. We have successfully developed the bone-targeted liposomes of linagliptin using an aspartic acid conjugate, that is poly (aspartic acid-co-lactide)-1,2-dipalmitoyl-sn-glycero-3-phospho ethanolamine (PAL-DPPE), which was prior synthesised and identified using FTIR and NMR. Liposomes were evaluated for particle size, encapsulation efficacy, drug loading and release study in addition to in vitro hydroxyapatite binding ability. To determine the anti-osteoporosis effect of liposomes, in vivo testing was performed in glucocorticoid-induced osteoporosis model in mice. Bone targeted liposomes of linagliptin having particle size of 281.7 nm and hydroxyapatite affinity of 89% significantly improved the bone architecture parameters and bone mineral density in micro-computed tomography analysis. Further, these liposomes positively modulated sclerostin, bone morphogenetic protein-2, receptor activator of nuclear factor kappa beta/osteoprotegerin ratio and other bone turnover biomarkers. The findings demonstrate that aspartic acid conjugate (PAL-DPPE)-based bone-targeted liposomes of linagliptin hold promise for the treatment of osteoporosis. Moreover, the possible mechanistic pathways involved here is Wnt and AMPK pathway.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408553","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}

引用次数: 0

Anti-GPC3 antibody and cell-penetrating peptide CPP44 dual-ligand modified liposomes for targeted delivery of arsenic trioxide in the treatment of hepatocellular carcinoma.

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-02-15 DOI: 10.1080/1061186X.2025.2461104

Congcong Lin, Jiamin Sun, Yun Yang, Xinyao Pan, Yifan Sun, Bin Sun, Chunli Gan

{"title":"Anti-GPC3 antibody and cell-penetrating peptide CPP44 dual-ligand modified liposomes for targeted delivery of arsenic trioxide in the treatment of hepatocellular carcinoma.","authors":"Congcong Lin, Jiamin Sun, Yun Yang, Xinyao Pan, Yifan Sun, Bin Sun, Chunli Gan","doi":"10.1080/1061186X.2025.2461104","DOIUrl":"10.1080/1061186X.2025.2461104","url":null,"abstract":"Arsenic trioxide (ATO), the active ingredient in Chinese arsenic, effectively inhibits hepatocellular carcinoma (HCC) cell growth, but its clinical application is limited by the lack of a targeted delivery system. Phosphatidylinositol proteoglycan 3 (GPC3) is specifically expressed in HCC, and CPP44 is a cell-penetrating peptide that targets HCC cells. Here, we developed a liposome incorporating ATO with dual surface modifications of anti-GPC3 antibody and CPP44. The system was firstly enriched and localised at the liver tumour site through passive targeting by EPR and active targeting by specific binding of anti-GPC3 antibody to GPC3 protein. CPP44 then facilitated ATO penetration into HCC cells. Specifically, we first employed computational modelling to demonstrate that the covalently-coupled antibody maintained its binding ability to the GPC3 antigen. Subsequent experimental assays revealed that Dl-ATO-Lp exhibited higher cell uptake rate and stronger tumour cell killing effect. In an HCC mouse model, Dl-ATO-Lp achieved effective tumour targeting, with a tumour inhibition rate of 63.43%. This dual-ligand liposome system enhances the targeted delivery and therapeutic efficacy of ATO, offering a promising direction for solid tumour therapy and advancing the clinical application of ATO.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066008","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}

引用次数: 0