Journal of Drug Targeting最新文献_第4页

Targeted immunomodulation in psoriasis: emerging progress on biologics and small molecules. 银屑病的靶向免疫调节：生物制剂和小分子的新进展。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-10-05 DOI: 10.1080/1061186X.2026.2738198

Rahul Kadiyan, Molly Maheshwari, S Latha, Ashish Dilip Sutar, Rahul Shukla, Robin Kumar, P K Sahoo, Beauty Behera

{"title":"Targeted immunomodulation in psoriasis: emerging progress on biologics and small molecules.","authors":"Rahul Kadiyan, Molly Maheshwari, S Latha, Ashish Dilip Sutar, Rahul Shukla, Robin Kumar, P K Sahoo, Beauty Behera","doi":"10.1080/1061186X.2026.2738198","DOIUrl":"10.1080/1061186X.2026.2738198","url":null,"abstract":"Psoriasis is a chronic immune-mediated inflammatory skin disorder that affects more than 125 million people worldwide. A dysregulation in the multiple immune signalling pathways involving innate and adaptive immune cells, leads to persistent inflammation and epidermal hyperproliferation in psoriasis. Hyperactivation of immune cells results in excessive production of proinflammatory cytokines, including interleukins and tumour necrosis factor-α (TNF-α), alongside increased secretion of antimicrobial peptides by keratinocytes and innate immune cells. This review examines the cytokine driven immunopathology of psoriasis and recent advances in targeted therapies. Current therapeutic strategies focusing on selective modulation of these pathways through biologic and small molecules are highlighted. Major advances on inhibitors targeting IL-17, IL-23, and JAK/TYK2 signalling pathways are also discussed. Emerging therapies such as sphingosine-1-phosphate (S1P) receptor modulators, RORγt inhibitors, and aryl hydrocarbon receptor (AhR) agonists have also demonstrated promising efficacy and safety, with significant improvements in psoriasis area and severity index (PASI) scores. A deeper understanding of psoriasis immunopathogenesis can transform treatment approaches from broad immunosuppression to precision-targeted therapies. Continued development of cytokine and signalling pathway specific agents is expected to improve long-term disease control, safety, and personalised patient outcomes.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-17"},"PeriodicalIF":4.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030707","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

Molecular mechanisms of resistance to KRAS^G12C inhibitors in NSCLC- from genomic evolution to TME adaptation. NSCLC对KRASG12C抑制剂耐药的分子机制——从基因组进化到TME适应

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-10-01 DOI: 10.1080/1061186X.2026.2741202

Simmy Mehta, Yugshree Vidhyarthi, Mercy Jacquiline, Neeru Singh

{"title":"Molecular mechanisms of resistance to KRASG12C inhibitors in NSCLC- from genomic evolution to TME adaptation.","authors":"Simmy Mehta, Yugshree Vidhyarthi, Mercy Jacquiline, Neeru Singh","doi":"10.1080/1061186X.2026.2741202","DOIUrl":"10.1080/1061186X.2026.2741202","url":null,"abstract":"The clinical breakthrough achieved with KRASG12C inhibitors is limited in therapeutic response by the remarkable adaptive capacity of KRAS-mutant tumours. The drug resistance emerges through a dynamic interplay between tumour intrinsic and micro-environmental mechanisms. At the cellular level, there may be a rebound of KRAS-dependent signalling due to secondary alterations within mutant KRAS or there may be the acquisition of co-mutations followed by activation of KRAS-independent bypass pathways to drive the therapeutic escape. The hypoxic tumour microenvironment (TME) also evolves to support cancer cell growth and exerts a critical influence on therapeutic efficacy. The desmoplastic stromal remodelling imposes substantial barrier to drug delivery and limits effective target engagement. Additionally, as a consequence of various genotoxic assaults, the dependence on DNA damage response (DDR) pathways increases under oncogenic and therapeutic pressure which is supported by aberrant expression of DDR proteins. KRAS stability and signalling output are also reinforced by proteostasis networks and endoplasmic reticulum stress responses, which collectively sustain tumour fitness during pharmacologic inhibition. In this Review, we synthesise emerging insights into the multi-layered mechanisms that constrain the efficacy of KRASG12C targeted therapies and discuss evolving therapeutic strategies designed to overcome adaptive resistance in KRAS mutant malignancies.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069649","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

Engineered exosomes for oral administration: breaking gastrointestinal barriers for disease therapy. 用于口服给药的工程外泌体：打破疾病治疗的胃肠道屏障。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-29 DOI: 10.1080/1061186X.2026.2733612

Ying Ma, Tong An, Pan Wu, Daqin Li, Runxuan Wang, Huijuan Song, Qiang Liu, Ningning He

{"title":"Engineered exosomes for oral administration: breaking gastrointestinal barriers for disease therapy.","authors":"Ying Ma, Tong An, Pan Wu, Daqin Li, Runxuan Wang, Huijuan Song, Qiang Liu, Ningning He","doi":"10.1080/1061186X.2026.2733612","DOIUrl":"10.1080/1061186X.2026.2733612","url":null,"abstract":"Extracellular vesicles (EVs) and exosomes are nanoscale vesicles from diverse biological sources, including animals, plants, and bacteria. Due to their pharmacological activity, high biosafety, and biocompatibility, they attract attention in intercellular signalling and therapeutic delivery. Oral administration is more convenient than invasive routes. Engineering strategies (surface modification, hybridisation, gastric acid-resistant encapsulation) significantly enhance gastrointestinal stability and targeting. This review summarises research progress of engineered EVs or exosomes for oral administration in disease treatment. We discuss exosomes from different sources, compare their biogenesis, isolation, purification, characterisation methods, examine engineering strategies for gastrointestinal stability, and summarise application potential. We place special emphasis on the clinical trials of oral exosome administration that have not yet obtained clinical approval, and further discuss the current challenges and prospects for clinical translation. Establishing unified production, quality control, and regulatory standards for exosomes in preclinical stage, analysing structural characteristics and mechanisms of crossing the gastrointestinal barrier, and combining with the quantitative analysis of exosomes in the gastrointestinal tract combining quantitative analysis of exosomes in the gut will help formulate more effective clinical translation strategies.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-16"},"PeriodicalIF":4.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969408","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

Stimuli-Responsive mesoporous silica nanoparticles for precision cancer therapy: design principles, cellular uptake, and translational perspectives. 刺激响应的介孔二氧化硅纳米颗粒用于精确的癌症治疗：设计原则，细胞摄取和转化的观点。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-29 DOI: 10.1080/1061186X.2026.2735989

Umar Abbasi, Md Saifuddin, Mahak Fatima, Garima Gupta, Khang Wen Goh, Amirhossein Sahebkar, Prashant Kesharwani

{"title":"Stimuli-Responsive mesoporous silica nanoparticles for precision cancer therapy: design principles, cellular uptake, and translational perspectives.","authors":"Umar Abbasi, Md Saifuddin, Mahak Fatima, Garima Gupta, Khang Wen Goh, Amirhossein Sahebkar, Prashant Kesharwani","doi":"10.1080/1061186X.2026.2735989","DOIUrl":"10.1080/1061186X.2026.2735989","url":null,"abstract":"Premature drug release in the systemic circulation or at off-target sites remains a major challenge in conventional drug delivery systems, often resulting in reduced therapeutic efficacy and increased systemic toxicity. Nanotechnology-based delivery platforms have emerged as promising strategies to address these limitations. Among them, mesoporous silica nanoparticles (MSNs) have attracted considerable attention due to their high surface area, tuneable pore size, large loading capacity, and considerable structural stability. These features enable efficient encapsulation and controlled delivery of therapeutic cargos. Recent advances in MSN engineering have focused on the development of stimuli-responsive systems capable of releasing drugs in response to specific internal or external triggers, such as pH variations, temperature, light, enzymatic activity, and redox conditions (e.g. glutathione). Such smart nanocarriers facilitate site-specific drug release while minimising off-target effects. This review highlights recent progress in the design and application of stimuli-responsive MSNs for cancer therapy. Particular emphasis is placed on mechanisms of intracellular uptake, factors influencing cellular internalisation, and strategies for controlled drug release. In addition, current insights into the biocompatibility and toxicity of MSNs are discussed to provide a comprehensive perspective on their translational potential in cancer nanomedicine.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-23"},"PeriodicalIF":4.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990029","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

Polyphenol-crosslinked green synthesis of mucoadhesive chitosan nanoparticle encapsulated with cisplatin for localised management of cervical cancer. 顺铂包封壳聚糖纳米粒多酚交联绿色合成用于宫颈癌的局部治疗。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-29 DOI: 10.1080/1061186X.2026.2735993

Ivy Saha, Tushar Kanti Rajwar, Rakesh Kumar Sahoo, Jitu Halder, Vineet Kumar Rai, Saurjit Mohapatra, Arijit Nandi, Salim Manoharadas, Jameel Al-Tamimi, Biswakanth Kar, Goutam Ghosh, Goutam Rath

{"title":"Polyphenol-crosslinked green synthesis of mucoadhesive chitosan nanoparticle encapsulated with cisplatin for localised management of cervical cancer.","authors":"Ivy Saha, Tushar Kanti Rajwar, Rakesh Kumar Sahoo, Jitu Halder, Vineet Kumar Rai, Saurjit Mohapatra, Arijit Nandi, Salim Manoharadas, Jameel Al-Tamimi, Biswakanth Kar, Goutam Ghosh, Goutam Rath","doi":"10.1080/1061186X.2026.2735993","DOIUrl":"10.1080/1061186X.2026.2735993","url":null,"abstract":"Chitosan (CS) nanoparticles have been widely investigated for cervical cancer (CC) therapy, with tripolyphosphate (TPP) commonly used as a crosslinker. This study explored ellagic acid (EA), a natural polyphenol with anticancer activity, as an alternative crosslinker for cisplatin-loaded EA-crosslinked CS nanoparticles (CisEANP) and compared them with cisplatin-loaded TPP-crosslinked CS nanoparticles (CisTPPNP). CisEANP showed a particle size (PS) of 260.9 ± 4.40 nm and zeta potential of +35 ± 1.30 mV, with spherical morphology and good mucoadhesiveness suitable for vaginal administration. Both formulations provided sustained cisplatin (Cis) release, with higher drug release from CisEANP. CisEANP significantly reduced HeLa cell viability compared with CisTPPNP and showed increased reactive oxygen species (ROS) generation and caspase activation. Antiangiogenic activity was confirmed by the chorioallantoic membrane (CAM) assay. In an Ehrlich ascites carcinoma (EAC)-induced CC mouse model, CisEANP and CisTPPNP reduced tumour volume by 1.23- and 1.49-fold, respectively, compared with disease control, with greater tumour regression observed for CisEANP. Histopathology supported the therapeutic findings, while X-ray imaging confirmed vaginal retention for up to 8 h. Overall, EA showed potential as a functional crosslinker for localised Cis delivery in CC.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-16"},"PeriodicalIF":4.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038933","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

Neuroprotective Effects of Nanocurcumin in Spinal Cord Injury: Modulation of Inflammatory and Inflammasome-Associated Signaling in an Integrated In Vivo, In Silico, and Machine-Learning Study. 纳米姜黄素在脊髓损伤中的神经保护作用：体内、计算机和机器学习综合研究中炎症和炎性体相关信号的调节

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-28 DOI: 10.1080/1061186X.2026.2741215

Seyyedeh Fahimeh Talebi, Jalal Mardaneh, Mohammad Matin Alishani, Abeer Ali Kadhim, Pasha Mosaed, Ako Mohammadi, Sajad Najafi, Jamal Majidpoor, Hamed Shoorei

{"title":"Neuroprotective Effects of Nanocurcumin in Spinal Cord Injury: Modulation of Inflammatory and Inflammasome-Associated Signaling in an Integrated In Vivo, In Silico, and Machine-Learning Study.","authors":"Seyyedeh Fahimeh Talebi, Jalal Mardaneh, Mohammad Matin Alishani, Abeer Ali Kadhim, Pasha Mosaed, Ako Mohammadi, Sajad Najafi, Jamal Majidpoor, Hamed Shoorei","doi":"10.1080/1061186X.2026.2741215","DOIUrl":"https://doi.org/10.1080/1061186X.2026.2741215","url":null,"abstract":"Spinal cord injury (SCI) triggers secondary neuroinflammatory and inflammasome-associated responses that contribute to tissue damage and functional impairment. This study evaluated nanocurcumin in experimental SCI using integrated experimental, computational, and exploratory machine-learning approaches. Adult male Wistar rats were allocated to Sham, SCI, or SCI + nanocurcumin groups. SCI was induced by T6 contusion, and nanocurcumin (50 mg/kg, intraperitoneally) was administered every 12 hours for 72 hours. Functional, histological, molecular, and inflammatory outcomes were assessed using BBB scoring, Luxol Fast Blue staining, immunofluorescence, RT-qPCR, and ELISA. SCI impaired locomotor function and myelin integrity and increased inflammasome-associated and inflammatory markers. Nanocurcumin significantly improved BBB scores, increased the LFB-positive myelinated area, and attenuated these molecular alterations. Tissue IL-1β, IL-18, HMGB1, and TLR4 levels were also reduced following nanocurcumin treatment compared with untreated SCI. Correlation and hierarchical clustering analyses demonstrated coordinated molecular-functional associations and separation of SCI from control and treated profiles. Exploratory Random Forest/SHAP analyses highlighted NF-κB, Caspase-1, NOX2, and NLRP3 as influential variables for group discrimination. Docking predicted favorable curcumin-target interactions, while MD simulations supported distinct conformational behavior of selected complexes. Overall, nanocurcumin was associated with attenuated inflammatory and inflammasome-associated responses and improved early functional and histological outcomes following SCI.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-19"},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069670","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

Graphene oxide as a potential drug delivery system: evaluation of biocompatibility in vivo. 氧化石墨烯作为一种潜在的药物传递系统：体内生物相容性评价。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-28 DOI: 10.1080/1061186X.2026.2737801

Tetiana Dumych, Solomiya Paryzhak, Nadia Skorokhyd, Svitlana Prylutska, Uwe Ritter, Yuriy Prylutskyy, Rostyslav Panchuk

{"title":"Graphene oxide as a potential drug delivery system: evaluation of biocompatibility in vivo.","authors":"Tetiana Dumych, Solomiya Paryzhak, Nadia Skorokhyd, Svitlana Prylutska, Uwe Ritter, Yuriy Prylutskyy, Rostyslav Panchuk","doi":"10.1080/1061186X.2026.2737801","DOIUrl":"10.1080/1061186X.2026.2737801","url":null,"abstract":"Graphene oxide (GO) has considerable potential as a highly efficient nanocarrier for drug delivery, but many toxicity studies have been limited to a single intravenous injection, which does not provide a complete picture of its biocompatibility in vivo. This study investigates the long-term, dose-related safety profile and systemic inflammatory responses to submicron-sized GO under a repeated-dose regimen relevant to drug-delivery applications. BALB/c mice received repeated intraperitoneal injections of unmodified GO sheets at cumulative doses of 10 mg/kg or 25 mg/kg, with longitudinal monitoring up to 60 days. The 10 mg/kg dose of GO was well tolerated, with no adverse changes in hematological parameters or biochemical markers of hepatic and renal function. In contrast, the 25 mg/kg cumulative dose was associated with a low-grade systemic inflammatory response, characterised primarily by increased circulating neutrophils. Serum biochemistry revealed a non-significant trend towards elevated aspartate aminotransferase activity, while creatinine levels remained unchanged. Overall, our findings delineate dose-related safety considerations for GO-based drug delivery design, validating the lower cumulative dose of 10 mg/kg as well tolerated. The intraperitoneal administration model may also provide a useful alternative for evaluating the systemic effects of GO while avoiding direct intravenous exposure.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038709","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

Biointerface-engineered gold and silver nanoparticles for skin cancer therapy: linking nano-biointerface design to therapeutic function and clinical translation. 生物界面工程金和银纳米粒子用于皮肤癌治疗：将纳米生物界面设计与治疗功能和临床转化联系起来。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-28 DOI: 10.1080/1061186X.2026.2737278

Aishani Vadi, Asiya Jahan, Urushi Rehman, Mohammed A S Abourehab, Garima Gupta, Khang Wen Goh, Prashant Kesharwani

{"title":"Biointerface-engineered gold and silver nanoparticles for skin cancer therapy: linking nano-biointerface design to therapeutic function and clinical translation.","authors":"Aishani Vadi, Asiya Jahan, Urushi Rehman, Mohammed A S Abourehab, Garima Gupta, Khang Wen Goh, Prashant Kesharwani","doi":"10.1080/1061186X.2026.2737278","DOIUrl":"10.1080/1061186X.2026.2737278","url":null,"abstract":"Skin cancer therapy continues to face challenges in achieving selective tumour targeting while limiting damage to healthy tissue. Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have emerged as versatile platforms for skin cancer treatment, but their therapeutic behaviour is strongly influenced by the nano-biointerface. This review critically examines how particle size, morphology, surface chemistry, ligand functionalization, and biomimetic coatings influence skin penetration, cellular uptake, tumour localisation, and therapeutic activity. The reviewed evidence indicates that AuNPs are particularly suited to photothermal and photodynamic therapies because their plasmonic properties enable localised light-mediated effects, whereas AgNPs exhibit prominent cytotoxic activity associated with reactive oxygen species generation and modulation of the tumour microenvironment. Biointerface engineering can further enable active targeting, improve colloidal stability, alter biodistribution, and integrate multiple therapeutic functions. However, reported improvements in therapeutic efficacy are accompanied by unresolved concerns regarding nanoparticle stability, reproducibility, long-term toxicity, biodistribution, and standardisation. Overall, the evidence indicates that nanoparticle performance cannot be considered independently of the nano-biointerface. Rational control of interfacial properties is therefore central to improving targeting precision and therapeutic performance, while standardised characterisation, mechanistic understanding, and systematic safety evaluation remain essential for clinical translation.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-15"},"PeriodicalIF":4.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989978","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

Bacterial outer membrane vesicles in colorectal cancer: interdomain communication hubs in pathogenesis and immunotherapy. 结直肠癌细菌外膜囊泡：发病机制和免疫治疗的领域间通讯枢纽。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-22 DOI: 10.1080/1061186X.2026.2735996

Marzieh Khaneshi, Roghayeh Faraji Akhijahani, Golnaz Mobayen, Sepideh Shadravan, Masoud Lahouty

{"title":"Bacterial outer membrane vesicles in colorectal cancer: interdomain communication hubs in pathogenesis and immunotherapy.","authors":"Marzieh Khaneshi, Roghayeh Faraji Akhijahani, Golnaz Mobayen, Sepideh Shadravan, Masoud Lahouty","doi":"10.1080/1061186X.2026.2735996","DOIUrl":"10.1080/1061186X.2026.2735996","url":null,"abstract":"The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs) - nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms - have emerged as critical long-range signalling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift towards exploiting next-generation probiotic and engineered OMVs as highly tuneable therapeutic platforms. By combining cutting-edge bioengineering strategies - such as biomimetic mineralisation to neutralise local tissue acidity and chemotherapeutic packaging - these nanovectors effectively reprogram the immunosuppressive tumour microenvironment (TME). Specifically, optimised OMVs modulate macrophage polarisation from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically 'cold' tumours 'hot'. Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-11"},"PeriodicalIF":4.7,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990018","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

A repurposed olmesartan-loaded hyaluronic acid-functionalised lecithin-chitosan nanoparticle hydrogel for enhanced topical delivery in diabetic wound healing. 奥美沙坦负载透明质酸功能化卵磷脂-壳聚糖纳米颗粒水凝胶用于增强糖尿病伤口愈合的局部递送。

IF 4.7 4区医学

Journal of Drug Targeting Pub Date : 2026-09-22 DOI: 10.1080/1061186X.2026.2733606

Walaa A El-Dakroury, Gihan F Asaad, Al-Aliaa M Sallam, Mohammed S Elballal, Mahmoud A ElRebehy, Fatma Sa'eed El-Tokhy, Ahmed E Elesawy, Manar Mohammed El Tabaa, Maram Mohammed El Tabaa, Rahma Mohamed Abuhegara, Aya Sabry Abdelmoneim Waly, Aya Hossam Zakaria, Asmaa Tharwat Elshabrawy, Ramy Sobhy, Mariham Rabea Boles, Aya Elsayed Fathy, Abdelrahman R Said

{"title":"A repurposed olmesartan-loaded hyaluronic acid-functionalised lecithin-chitosan nanoparticle hydrogel for enhanced topical delivery in diabetic wound healing.","authors":"Walaa A El-Dakroury, Gihan F Asaad, Al-Aliaa M Sallam, Mohammed S Elballal, Mahmoud A ElRebehy, Fatma Sa'eed El-Tokhy, Ahmed E Elesawy, Manar Mohammed El Tabaa, Maram Mohammed El Tabaa, Rahma Mohamed Abuhegara, Aya Sabry Abdelmoneim Waly, Aya Hossam Zakaria, Asmaa Tharwat Elshabrawy, Ramy Sobhy, Mariham Rabea Boles, Aya Elsayed Fathy, Abdelrahman R Said","doi":"10.1080/1061186X.2026.2733606","DOIUrl":"10.1080/1061186X.2026.2733606","url":null,"abstract":"A novel topical nanocarrier-based hydrogel system incorporating olmesartan medoxomil (OLM) was designed to enhance diabetic wound healing. OLM was efficiently encapsulated within lecithin-chitosan hybrid nanoparticles (LCNPs) and functionalized with hyaluronic acid (HA) to improve bioadhesion, biocompatibility, and sustained release. The optimized OLM-HA-LCNPs exhibited a nanoscale size of 324.28 ± 5.71 nm, a negative zeta potential (-39.64 ± 3.2 mV), and a high entrapment efficiency of 89.86 ± 3.15 %. In vitro release studies demonstrated a controlled, biphasic OLM release following Weibull kinetics, confirming diffusion erosion-controlled release behavior. Incorporation into a hydrogel base preserved pseudoplastic rheology, optimal pH (6.3 ± 0.2), and superior spreadability (35.26 cm2). In streptozotocin-induced diabetic rats, the OLM-HA-LCNP hydrogel produced 93.5% wound closure after 14 days, compared with 87.6%, 77.1%, and 90.8% for the marketed reference, plain HA-LCNPs, and OLM-pure treatments, respectively. OLM-HA-LCNP hydrogel also increased CAT, SOD, and GSH levels by 2.7, 1.45, and 2.16 fold, respectively, and reduced MDA levels by 77% compared with diabetic controls. Histological and immunohistochemical findings further demonstrated improved epidermal regeneration, collagen deposition, and normalization of VEGF and MMP-9 expression. Collectively, these findings demonstrate that the OLM-HA-LCNPs hydrogel efficiently improves topical OLM delivery and therapeutic performance in diabetic wound healing.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-24"},"PeriodicalIF":4.7,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969224","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