Journal of Drug Targeting最新文献_第8页

RNA therapeutics and their delivery methods: a paradigm for haemophilia management. RNA疗法及其递送方法：血友病管理的范例。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-01 Epub Date: 2026-05-13 DOI: 10.1080/1061186X.2026.2638330

Ali Rajabi Zangi, Ala Amiri, Fatemeh Eskandari, Pouya Pazooki, Hamid Reza Heidari, Hamed Hamishehkar, Yousef Javadzadeh

{"title":"RNA therapeutics and their delivery methods: a paradigm for haemophilia management.","authors":"Ali Rajabi Zangi, Ala Amiri, Fatemeh Eskandari, Pouya Pazooki, Hamid Reza Heidari, Hamed Hamishehkar, Yousef Javadzadeh","doi":"10.1080/1061186X.2026.2638330","DOIUrl":"10.1080/1061186X.2026.2638330","url":null,"abstract":"Haemophilia management is currently undergoing a paradigm shift from traditional protein replacement to RNA modalities and their delivery. This review provides a critical analysis of RNA-based therapeutics (specifically small interfering RNA (siRNA), mRNA and CRISPR/Cas9) as a versatile paradigm distinct from DNA ones. We synthesise clinical and preclinical data to contrast these modalities: siRNA strategies (e.g. fitusiran) have indicated ∼90% reductions in bleeding rates by rebalancing haemostasis independent of factor deficiency; lipid nanoparticles (LNPs)-mRNA platforms offer tuneable, transient factor production without genomic integration risks; and CRISPR-based editing aims for permanent correction (up to 170% coagulation factor IX, FIX expression in preclinical studies) but necessitates rigorous monitoring for off-target effects. Crucially, this article dissects the non-viral delivery landscape determining the clinical viability of these cargos. We evaluate LNPs as the current clinical gold standard for hepatic delivery, contrasting them against emerging polymeric systems, aptamer conjugates and exosomes designed to overcome rate-limiting barriers such as endosomal entrapment and renal clearance. By juxtaposing the immunogenic limitations of viral vectors, we conclude that next-generation RNA therapeutics, enabled by LNPs and GalNAc-conjugation, offer a strategic pathway to overcome the durability gap observed in haemophilia A and expand treatment access to patients currently excluded by viral seroprevalence.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1394-1413"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868504","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

Design and evaluation of a novel peptide-EV complex for targeted Alzheimer's disease therapy. 一种针对阿尔茨海默病治疗的新型肽- ev复合物的设计和评价。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-28 DOI: 10.1080/1061186X.2026.2724027

Varsha Birendra Singh, Raja Natesan Sella

{"title":"Design and evaluation of a novel peptide-EV complex for targeted Alzheimer's disease therapy.","authors":"Varsha Birendra Singh, Raja Natesan Sella","doi":"10.1080/1061186X.2026.2724027","DOIUrl":"10.1080/1061186X.2026.2724027","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder that involves the formation of amyloid-β (Aβ) aggregates, and the development of targeted therapeutic strategies is needed. In the current work, we report the rational design of H102-CP05, a 22-residue chimeric peptide that integrates the β-sheet breaker peptide H102 with the CD63-targeting anchor CP05 to enable extracellular vesicle (EV)-mediated delivery of an Aβ-inhibitory payload. Computational analysis confirmed favourable physicochemical properties and a non-allergenic profile. In silico immunogenicity assessment and C-IMMSIM simulation demonstrated a low risk of anti-drug antibody formation under chronic dosing conditions. Homology modelling and HADDOCK docking (score: -147.2 ± 4.6) predicted a computationally favourable CD63 binding configuration, while 100 ns molecular dynamics simulations confirmed structural stability in both aqueous and EV-mimetic lipid bilayer environments. In vitro cytotoxicity against HEK-293 cells revealed no significant toxicity (10-100 µM). Zebrafish embryo studies indicated acceptable developmental safety at lower concentrations, with concentration-dependent bradycardia observed at higher doses warranting further cardiovascular evaluation. Thioflavin T fluorescence assays demonstrated dose-dependent inhibition of Aβ fibrillation, with near-complete suppression at 100 µM. These findings collectively support H102-CP05 as a promising EV-displayed therapeutic candidate for AD.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-19"},"PeriodicalIF":4.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793978","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

Pulmonary delivery of silk fibroin peptides dry powder inhalers for idiopathic pulmonary fibrosis. 丝素肽干粉吸入器肺输送治疗特发性肺纤维化。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-27 DOI: 10.1080/1061186X.2026.2680984

Jinmei Ni, Mengxing Chen, Zhenming Wu, Qian Zhang, Lihong Wang, Xin Che

{"title":"Pulmonary delivery of silk fibroin peptides dry powder inhalers for idiopathic pulmonary fibrosis.","authors":"Jinmei Ni, Mengxing Chen, Zhenming Wu, Qian Zhang, Lihong Wang, Xin Che","doi":"10.1080/1061186X.2026.2680984","DOIUrl":"10.1080/1061186X.2026.2680984","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a common disease of pulmonary fibrosis with an increasing incidence. Silk fibroin peptides (SFPs) are bioactive substances rich in essential amino acids and possess antioxidant and anti-inflammatory properties; however, their application is limited by drawbacks such as low bioavailability and susceptibility to protein degradation. In this study, spray-drying technology was employed to prepare a silk fibroin peptides dry powder inhaler (SFPs-DPI), followed by characterisation of its physicochemical properties and preliminary in vitro and in vivo studies. The results showed that the yield of SFPs-DPI was 56.86 ± 1.80%, the Carr's index was 25.64 ± 1.71%, the aerodynamic diameter was 2.26 ± 0.04 μm, the moisture content of 0.74%, and the emptying rate was 93 ± 1.61%. In vitro studies demonstrated that SFPs-DPI exhibits good cellular biocompatibility and antioxidant activity. In vivo pharmacodynamic results showed that SFPs-DPI reduced inflammatory infiltration and collagen fibre deposition in the lungs of IPF mice and reduced the expression of type I collagen and α-SMA in lung tissue. Therefore, the physicochemical properties of the SFPs-DPI prepared in this study meet the relevant requirements for dry powder inhalation formulations, providing a preliminary reference for research related to IPF treatment.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-17"},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812787","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

Mitigating breast cancer with intratumoral in situ pH-responsive abemaciclib-loaded novasome hydrogel. 用瘤内原位ph响应的abemaciclib负载Novasome水凝胶缓解乳腺癌。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-25 DOI: 10.1080/1061186X.2026.2718352

Maha M Ghalwash, Randa Mohammed Zaki, Obaid Afzal, Rawan Bafail, Mary Girgis Shahataa, Waad A Samman, Amr Gamal Fouad, Sherif Faysal Abdelfattah Khalil, Shaimaa El-Housiny

{"title":"Mitigating breast cancer with intratumoral in situ pH-responsive abemaciclib-loaded novasome hydrogel.","authors":"Maha M Ghalwash, Randa Mohammed Zaki, Obaid Afzal, Rawan Bafail, Mary Girgis Shahataa, Waad A Samman, Amr Gamal Fouad, Sherif Faysal Abdelfattah Khalil, Shaimaa El-Housiny","doi":"10.1080/1061186X.2026.2718352","DOIUrl":"10.1080/1061186X.2026.2718352","url":null,"abstract":"Abemaciclib (AMC) is a selective CDK4/6 inhibitor widely utilised for breast cancer therapy; however, its efficacy is compromised by poor bioavailability and low aqueous solubility. This study aimed to enhance the sustained release, targeting, and efficacy of AMC via developing an intratumoral, in situ pH-responsive AMC-loaded novasome (IPANF) hydrogel. The optimal AMC-novasome was tailored using Design-Expert® software and subsequently incorporated into a chitosan/glyceryl monooleate mixture to develop IPANF. The in vivo anti-tumour efficacy and safety profile of the IPANF were evaluated using an Ehrlich ascites carcinoma model. Within 24 h, the IPANF formulation exhibited a significantly sustained drug release by 65.31% compared to the free AMC suspension. The intratumoral IPANF resulted in a profound 96.08% reduction in tumour volume, a 70.46% recovery in body weight, and a suppression of the CA 15-3 and CA 27-29 levels by 92.66% and 91.23%, respectively. Notably, a 100% survival rate was observed in the intratumoral IPANF group. Histopathological assessments firmly validated the superior therapeutic efficacy of the intratumoral IPANF hydrogel. Furthermore, the intratumoral IPANF formulation demonstrated an excellent safety profile. These findings underscore the clinical potential of the intratumoral IPANF hydrogel as a highly efficient, localised, and safe platform for advanced breast cancer treatment.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":4.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712687","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

Folic acid-functionalized PLGA-cystamine nanoparticles for glutathione-responsive capecitabine delivery in pancreatic cancer: in vitro and in vivo evaluation. 叶酸功能化的plga -胱胺纳米颗粒用于谷胱甘肽响应卡培他滨在胰腺癌中的递送：体外和体内评估。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-20 DOI: 10.1080/1061186X.2026.2716722

Abhay Dev Tripathi, Soumya Katiyar, Vivek K Chaturvedi, Anurag Kumar Singh, Abha Mishra

{"title":"Folic acid-functionalized PLGA-cystamine nanoparticles for glutathione-responsive capecitabine delivery in pancreatic cancer: in vitro and in vivo evaluation.","authors":"Abhay Dev Tripathi, Soumya Katiyar, Vivek K Chaturvedi, Anurag Kumar Singh, Abha Mishra","doi":"10.1080/1061186X.2026.2716722","DOIUrl":"https://doi.org/10.1080/1061186X.2026.2716722","url":null,"abstract":"Due to high systemic toxicity associated with conventional chemotherapy and limited drug accumulation at the tumour site, pancreatic cancer is still challenging to eliminate. To improve the intracellular transport of capecitabine, a glutathione-responsive nanocarrier system based on poly(lactic-co-glycolic acid) (PLGA) was designed. PLGA coupled with cystamine was used to create the nanoformulation, which introduced disulphide bonds that are stable in extracellular environments but cleaved in a reductive intracellular environment enriched with glutathione. This redox-sensitive mechanism enables rapid drug release specifically within cancer cells. The nanoparticle surface was functionalised with folic acid to promote folate receptor-mediated endocytosis, which is often overexpressed on pancreatic cancer, thereby further enhancing cellular uptake. DLS and TEM Microscopy confirmed a consistent nanoparticle size of FoA-PLGA-Cys-CAP 261.3 ± 2.8 nm with uniform shape, indicating suitability for therapeutic delivery. In vitro cytotoxicity studies showed an IC50 value of 77.52 ± 1.33 μg/mL and increased reactive oxygen species generation in treated cells. For in vivo evaluation, PANC1 cells were subcutaneously implanted to establish a pancreatic tumour model. Over 12 days, tumour size increased from 20.617 mm2 to 57.71 mm2. Following 10 days of treatment with the nanoformulation, tumour size significantly decreased from 57.71 mm2 to 43.099 mm2, demonstrating promising therapeutic efficacy.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-13"},"PeriodicalIF":4.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794019","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

Functionalized ZnS quantum dots as cancer theranostics: a cornerstone for precision onco-targeting. 功能化ZnS量子点作为癌症治疗：精确肿瘤协同靶向的基石。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-18 DOI: 10.1080/1061186X.2026.2718337

Dipak B Bari, Chandrakantsing V Pardeshi

{"title":"Functionalized ZnS quantum dots as cancer theranostics: a cornerstone for precision onco-targeting.","authors":"Dipak B Bari, Chandrakantsing V Pardeshi","doi":"10.1080/1061186X.2026.2718337","DOIUrl":"10.1080/1061186X.2026.2718337","url":null,"abstract":"Cancer is among the leading causes of death globally. Early diagnosis and therapy provide cancer patients with the highest chance of survival. Despite recent significant advances in understanding the complex pathways that contribute to cancer progression and metastasis, researchers are still unable to adequately treat cancer progressing to many crucial organs. As cancer cells and tumour microenvironments are highly complex, the mechanisms of tumour invasion, tumour development, and metastasis remain incompletely understood. Therefore, to grasp the complex molecular information behind biological behaviour of tumours, novel technologies for cancer detection and real-time observation are urgently needed. Quantum dots (QDs) are indeed luminous semiconductor materials in the nanometric size range. Considering their unique optical traits including excellent luminescence, simultaneous acquisition of numerous signals, stability over time, and tunable emission spectra, QDs are appealing as possible cancer theranostic devices. Zinc sulphide (ZnS) QDs are frequently employed as a cornerstone for precision onco-targeting owing to their high quantum yield, low toxicity, biocompatibility, and versatility for diverse surface modifications. ZnS QDs are now showing great promise for cancer bioimaging and anticancer drug delivery. The present review describes the frontiers of surface modifications and theranostic applications of ZnS QDs in the treatment of various cancers.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-21"},"PeriodicalIF":4.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712705","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

Carrier-free nanoparticles for cancer therapy: assembly strategies, therapeutic applications, and clinical translation. 无载体纳米颗粒用于癌症治疗：组装策略，治疗应用，和临床翻译。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-18 DOI: 10.1080/1061186X.2026.2718348

Ahequeli Gemingnuer, Hailing Wang, Rui Yin, Shujun Xu, Xin Meng

{"title":"Carrier-free nanoparticles for cancer therapy: assembly strategies, therapeutic applications, and clinical translation.","authors":"Ahequeli Gemingnuer, Hailing Wang, Rui Yin, Shujun Xu, Xin Meng","doi":"10.1080/1061186X.2026.2718348","DOIUrl":"10.1080/1061186X.2026.2718348","url":null,"abstract":"Carrier-free nanoparticles have emerged as a promising class of nanomedicines for cancer therapy, characterised by ultrahigh drug-loading capacity, reduced dependence on inert carriers, and enhanced therapeutic efficiency. Diverse design strategies, including molecular self-assembly, covalent prodrug conjugation, and stimuli-responsive construction, have enabled the development of structurally versatile and functionally integrated carrier-free nanoplatforms. These systems exhibit improved physicochemical properties, enhanced tumour accumulation, and multifunctional therapeutic capabilities. However, existing reviews have mainly focused on specific assembly strategies or individual therapeutic applications, while a systematic understanding linking nanoparticle design, tumour-specific responses, and clinical translation remains insufficient. This review summarises recent advances in the design and fabrication of carrier-free nanoparticles and provides an integrated analysis of their assembly mechanisms, physicochemical characteristics, and therapeutic applications across diverse cancer types, including breast, lung, and liver cancers. In addition, this review comparatively discusses different therapeutic modalities, including chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, ferroptosis, and immunotherapy, with emphasis on their advantages, limitations, and translational potential. Current clinical progress, patent trends, and future challenges are also analysed to provide insights into the rational design and clinical development of carrier-free nanoparticles for cancer therapy.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-29"},"PeriodicalIF":4.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759852","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

Cathepsin B-activated vitamin E prodrugs target cancer stem cells and enhance chemotherapy response in triple-negative breast cancer with minimal cardiotoxicity. 组织蛋白酶b激活的维生素E前药靶向癌症干细胞并增强三阴性乳腺癌的化疗反应，且心脏毒性最小。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-10 DOI: 10.1080/1061186X.2026.2704903

Raghu Pandurangi, Marco Tomasetti, Sekar T Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput

{"title":"Cathepsin B-activated vitamin E prodrugs target cancer stem cells and enhance chemotherapy response in triple-negative breast cancer with minimal cardiotoxicity.","authors":"Raghu Pandurangi, Marco Tomasetti, Sekar T Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput","doi":"10.1080/1061186X.2026.2704903","DOIUrl":"10.1080/1061186X.2026.2704903","url":null,"abstract":"Triple-negative breast cancer (TNBC) remains difficult to treat because of therapeutic resistance, cancer stem cell (CSC) enrichment, and constitutive NF-κB activation. We developed a new therapeutic strategy, A Priori Activation of Apoptosis Pathways (AAAPT), to restore apoptotic competence before chemotherapy by suppressing survival signaling and reactivating programmed cell death. Since TNBC and CSC-enriched populations overexpress Cathepsin B and exhibit lysosomal and mitochondrial vulnerabilities, we designed Cathepsin B-cleavable vitamin E analogues (AMP-001/002/003) that selectively release the active pharmacophore within tumor cells. AMP-001/002/003 demonstrated selective cytotoxicity toward Cathepsin B-positive TNBC cells, inhibited mammosphere formation, and spared normal epithelial cells and human iPSC-derived cardiomyocytes. AMP-001 synergized strongly with doxorubicin, markedly reducing its effective IC₅。 while restoring chemosensitivity. In TNBC xenograft models, AMP-001 significantly reduced tumor burden without overt systemic or cardiac toxicity. Collectively, these findings establish AAAPT as a tumor-selective chemosensitization platform that targets CSCs, reverses NF-κB-mediated resistance, exploits lysosomal-mitochondrial vulnerabilities, and expands the therapeutic index of doxorubicin by maintaining antitumor efficacy while reducing cardiotoxicity.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-15"},"PeriodicalIF":4.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591964","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

TRAIL PLGA/Gelucire 48/16 and exosome carrier systems enhance anti-tumour efficacy by enabling autophagic motility. TRAIL PLGA/Gelucire 48/16和外泌体载体系统通过激活自噬运动来增强抗肿瘤功效。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-09 DOI: 10.1080/1061186X.2026.2714872

Aslihan Kucuk, Gulen Melike Demirbolat, Ozge Cevik

{"title":"TRAIL PLGA/Gelucire 48/16 and exosome carrier systems enhance anti-tumour efficacy by enabling autophagic motility.","authors":"Aslihan Kucuk, Gulen Melike Demirbolat, Ozge Cevik","doi":"10.1080/1061186X.2026.2714872","DOIUrl":"10.1080/1061186X.2026.2714872","url":null,"abstract":"TRAIL is a potent anticancer protein that selectively reduces the viability of malignant cells but is limited clinically by its short half-life. This study developed novel TRAIL-loaded drug carrier systems to prolong its mean residence time, consequently enhance its biological activity and enhance therapeutic efficacy in breast cancer, and evaluate tumour targeting and modulation of apoptotic and autophagic pathways in vitro and in vivo. TRAIL-loaded carrier systems were prepared using PLGA/Gelucire 48/16 nanoparticles and exosome-based formulations. Following physicochemical characterisation, biological effects were assessed in MDA-MB-231 cells and an EAC mouse tumour model, with cellular responses analysed by flow cytometry and qPCR. Histopathological assessments included HE staining, TUNEL assay, and Ki-67 IHC. Both formulations significantly suppressed cell viability and enhanced apoptosis in MDA-MB-231 cells. Treatment with these carrier systems upregulated the expression of Caspase-3 and LC3B genes in-vitro and in mouse tumour tissues, indicating activation of apoptotic and autophagic pathways. In the EAC tumour model, TRAIL-loaded formulations reduced tumour growth, decreased the Ki-67 proliferation index, and induced marked tumour regression. Encapsulation of TRAIL in PLGA/Gelucire 48/16 or exosome-based carriers enhances its stability and antitumor activity, highlighting the potential of these carrier platforms to improve TRAIL-encapsulated biotechnological therapeutics for breast cancer treatment.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673770","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

Formulation and evaluation of etoposide-loaded dextran polymeric nanoparticles fabricated with hyaluronic acid for the treatment of colorectal cancer using network pharmacology, in-silico, in-vitro, and in-vivo approaches. 透明质酸制备的依托泊苷负载右旋糖酐聚合物纳米颗粒的配方和评价，用于网络药理学、硅内、体外和体内方法治疗结直肠癌。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-08-05 DOI: 10.1080/1061186X.2026.2709768

Hrushikesh Wagh, Sankha Bhattacharya, Preeti Chidambar Sangave, Ranajit Nivrutti Shinde, Suprit D Saoji

{"title":"Formulation and evaluation of etoposide-loaded dextran polymeric nanoparticles fabricated with hyaluronic acid for the treatment of colorectal cancer using network pharmacology, in-silico, in-vitro, and in-vivo approaches.","authors":"Hrushikesh Wagh, Sankha Bhattacharya, Preeti Chidambar Sangave, Ranajit Nivrutti Shinde, Suprit D Saoji","doi":"10.1080/1061186X.2026.2709768","DOIUrl":"10.1080/1061186X.2026.2709768","url":null,"abstract":"Etoposide (ETP), a Biopharmaceutics Classification System class IV drug with poor aqueous solubility, demonstrates limited therapeutic efficacy against colorectal cancer (CRC) because of inferior absorption and off-target effects. To deliver drugs specifically to cancer cells that overexpress CD44, this study developed hyaluronic acid (HA)-functionalized dextran (DEX) polymeric nanoparticles (ETP-DEX-HA-NPs). Optimised nanoparticles (174.7 ± 3.2 nm, -12.83 ± 1.1 mV) demonstrated significant entrapment efficiency (62.75 ± 2.32%) and drug loading (55.64 ± 3.86%), with partial amorphization validated by FTIR, XRD, Raman, NMR and DSC analyses. The formulation exhibited prolonged, pH-responsive release, markedly improved solubility (p < 0.05), and greater cytotoxicity in HCT-116 cells (IC50: 6.83 ± 0.35 µg/mL compared to 41.89 ± 1.02 µg/mL for free ETP). It facilitated CD44-mediated uptake, enhanced apoptosis, induced G2/M arrest, elevated ROS production and inhibited migration while preserving biocompatibility. Network pharmacology and molecular docking identified key interactions with CRC-related targets (e.g. TOP2A, BCL2). ETP-DEX-HA-NPs offer a promising, targeted nanoplatform that addresses ETP's limitations, boosting therapeutic efficacy and safety for CRC treatment.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-45"},"PeriodicalIF":4.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620249","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