Journal of Drug Targeting最新文献

Local delivery of ibrutinib by folate receptor-mediated targeting PLGA-PEG nanoparticles to glioblastoma multiform: in vitro and in vivo studies. 叶酸受体介导的靶向PLGA-PEG纳米颗粒对多形性胶质母细胞瘤的局部递送伊鲁替尼：体外和体内研究

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub 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":"1026-1041"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","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

The role of green synthesis metal and metal oxide nanoparticles in oral cancer therapy: a review. 绿色合成金属和金属氧化物纳米颗粒在口腔癌治疗中的作用综述。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-02-08 DOI: 10.1080/1061186X.2025.2461091

Songlin Zhou, Yutao Qin, Anwen Lei, Hai Liu, Yi Sun, Jue Zhang, Chao Deng, Yu Chen

{"title":"The role of green synthesis metal and metal oxide nanoparticles in oral cancer therapy: a review.","authors":"Songlin Zhou, Yutao Qin, Anwen Lei, Hai Liu, Yi Sun, Jue Zhang, Chao Deng, Yu Chen","doi":"10.1080/1061186X.2025.2461091","DOIUrl":"10.1080/1061186X.2025.2461091","url":null,"abstract":"There are 275,000 new cases of oral cancer (OC) per year, making it the sixth most common cancer in the world. Severe adverse effects, including loss of function, deformity, and systemic toxicity, are familiar with traditional therapies such as radiation, chemotherapy, and surgery; due to their unique properties, nanoparticles (NPs) have emerged as a superior alternative over chemo/radiotherapy and surgery due to their targeting capability, bioavailability, compatibility, and high solubility. Due to their unique properties, metallic NPs have garnered significant attention in OC control. In addition to the fact that metal NPs may be harmful to human cells, the reactive chemicals used to make them pose the same risk, which limits their use in medicine. Green synthesis (GS) is a novel strategy that uses biological materials like yeast, bacteria, fungi, and plant extracts. Compared to more traditional chemical synthesis processes, these are more environmentally benign and manageable for living organisms. This article summarises the GS of NPs made of metals and metal oxides and their anticancer effects on OC. The method's potential benefits and drawbacks in advancing metallic NPs' GS and shaping OC therapy's future were also discussed.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"853-876"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066013","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

Exploring the potential of ferulic acid-loaded nanostructured lipid carriers: angiotensin inhibition via docking, formulation and pharmacokinetic and pharmacodynamics studies. “探索阿魏酸负载纳米结构脂质载体的潜力：通过对接、配方、药代动力学和药效学研究抑制血管紧张素”。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-01-29 DOI: 10.1080/1061186X.2025.2453743

Preeti Rajabhau Meshram, Nisharani Sudhakar Ranpise

{"title":"Exploring the potential of ferulic acid-loaded nanostructured lipid carriers: angiotensin inhibition via docking, formulation and pharmacokinetic and pharmacodynamics studies.","authors":"Preeti Rajabhau Meshram, Nisharani Sudhakar Ranpise","doi":"10.1080/1061186X.2025.2453743","DOIUrl":"10.1080/1061186X.2025.2453743","url":null,"abstract":"Ferulic acid (FA) is a natural phenolic compound that has been documented for its antioxidant properties and potential in managing hypertension. However, its use is limited due to poor solubility and permeability (BCS Class IV classification). To overcome this, nanostructured lipid carriers (NLCs) of FA were developed using the emulsification probe sonication technique, with formulation optimized through Box-Behnken design. The optimized FA-NLCs (F12) demonstrated a particle size of 103.4 nm, zeta potential of -43.6 mV, polydispersity index of 0.531, and entrapment efficiency of 88.9%. Key Findings of the research manifested, that during in-vitro release studies, FA-NLCs showed sustained release action (40.34% over 24 h) compared to plain FA (103.13% in 4 h). Pharmacokinetics of FA-NLC suggested that increased Cmax by 2.6-fold, AUC by 1.9-fold, and half-life significantly (p < .001), also Pharmacodynamics revealed that FA-NLCs reduced blood pressure more effectively (39.9 mmHg vs. 30.8 mmHg for plain FA; p < .001). Furthermore, FA-NLC was showing successful intestinal uptake through lymphatic absorption via clathrin-mediated endocytosis, bypassing first-pass metabolism, hence showed enhancement in bioavailability, Thus the study concluded that FA-NLCs significantly improve therapeutic efficacy and sustained blood pressure reduction compared to plain FA.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"952-974"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971053","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

Interactions and communications in lung tumour microenvironment: chemo/radiotherapy resistance mechanisms and therapeutic targets. 肺肿瘤微环境中的相互作用和通讯：化疗/放疗耐药机制和治疗靶点。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-01-22 DOI: 10.1080/1061186X.2025.2453730

Yuan Feng, Ying Jiang, Lin Yang, Danni Lu, Ning Li, Qun Zhang, Haiyan Yang, Huiyuan Qin, Jiaxin Zhang, Xinyun Gou, Feng Jiang

{"title":"Interactions and communications in lung tumour microenvironment: chemo/radiotherapy resistance mechanisms and therapeutic targets.","authors":"Yuan Feng, Ying Jiang, Lin Yang, Danni Lu, Ning Li, Qun Zhang, Haiyan Yang, Huiyuan Qin, Jiaxin Zhang, Xinyun Gou, Feng Jiang","doi":"10.1080/1061186X.2025.2453730","DOIUrl":"10.1080/1061186X.2025.2453730","url":null,"abstract":"The lung tumour microenvironment (TME) is composed of various cell types, including cancer cells, stromal and immune cells, as well as extracellular matrix (ECM). These cells and surrounding ECM create a stiff, hypoxic, acidic and immunosuppressive microenvironment that can augment the resistance of lung tumours to different forms of cell death and facilitate invasion and metastasis. This environment can induce chemo/radiotherapy resistance by inducing anti-apoptosis mediators such as phosphoinositide 3-kinase (PI3K)/Akt, signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB), leading to the exhaustion of antitumor immunity and further resistance to chemo/radiotherapy. In addition, lung tumour cells can resist chemo/radiotherapy by boosting multidrug resistance mechanisms and antioxidant defence systems within cancer cells and other TME components. In this review, we discuss the interactions and communications between these different components of the lung TME and also the effects of hypoxia, immune evasion and ECM remodelling on lung cancer resistance. Finally, we review the current strategies in preclinical and clinical studies, including the inhibition of checkpoint molecules, chemoattractants, cytokines, growth factors and immunosuppressive mediators such as programmed death 1 (PD-1), insulin-like growth factor 2 (IGF-2) for targeting the lung TME to overcome resistance to chemotherapy and radiotherapy.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"817-836"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006355","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 and therapeutic insight into ER stress signalling in NSCLC. 内质网应激信号在非小细胞肺癌中的分子和治疗作用。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-02-14 DOI: 10.1080/1061186X.2025.2461105

Aastha Jadhav, Arjun Menon, Kush Gupta, Neeru Singh

引用次数: 0

Pseudo-ternary phase diagram based PEGylated nano-dispersion of linezolid to promote wound regeneration: an in vitro and in vivo evaluation. 基于伪三元相图的聚乙二醇化奈利唑胺纳米分散体促进伤口再生：体外和体内评价。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-02-12 DOI: 10.1080/1061186X.2025.2461093

Bani Kumar Jana, Ishita Singha, Nusalu Puro, Rinku Baishya, Rajat Subhra Dutta, Mohini Singh, Bhaskar Mazumder

{"title":"Pseudo-ternary phase diagram based PEGylated nano-dispersion of linezolid to promote wound regeneration: an in vitro and in vivo evaluation.","authors":"Bani Kumar Jana, Ishita Singha, Nusalu Puro, Rinku Baishya, Rajat Subhra Dutta, Mohini Singh, Bhaskar Mazumder","doi":"10.1080/1061186X.2025.2461093","DOIUrl":"10.1080/1061186X.2025.2461093","url":null,"abstract":"Open wounds are prone to bacterial infiltration mostly resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), which affects healing of open wounds. Topical linezolid nano-dispersion using essential oils as nanoemulgel can increase solubility of drug and bypass side-effects like GI-irritation of oral administration. Pseudo-ternary phase diagram was built to optimise nanoemulsion. Surfactant/co-surfactant mixture (3:1), deionised water and Oilmix (4:1) with drug were vortexed and then ultrasonicated. 1% carbopol gel of optimised nanoemulsion was prepared and characterised, exposed to antimicrobial study, cytocompatibility study using HEK293 cell-line, and in vivo wound healing study using rat excision model. Histological study was performed to confirm growth of stratum corneum. Optimised formulation has particle size (244.6 ± 178.66 nm), polydispersity index (25%), entrapment efficiency (92.3 ± 3.38%) and in vitro drug release (87.58 ± 4.16%) best fitted in Korsmeyer-Peppas kinetics model. Nanoemulgel F6 (0.2%w/w) was found with viscosity of 5345 ± 6 cP constituting a very excellent antimicrobial effect against MRSA. HEK293 cells had shown good cytocompatibility with formulation. The wound contraction rate was 99.66 ± 0.57% at day 15 on daily application of nanoemulgel and stratum corneum was almost fully regenerated. The developed nanoemulgel has potential antimicrobial efficacy and can promote wound healing.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"989-1003"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074505","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, optimisation, and evaluation of Lornoxicam-loaded Novasomes for targeted ulcerative colitis therapy: in vitro and in vivo investigations. 含氯诺昔康的novasome靶向治疗溃疡性结肠炎的处方、优化和评价：体外和体内研究。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-01-25 DOI: 10.1080/1061186X.2025.2456929

Asmaa Badawy Darwish, Abeer Salama, Inas Essam Ibrahim Al-Samadi

{"title":"Formulation, optimisation, and evaluation of Lornoxicam-loaded Novasomes for targeted ulcerative colitis therapy: in vitro and in vivo investigations.","authors":"Asmaa Badawy Darwish, Abeer Salama, Inas Essam Ibrahim Al-Samadi","doi":"10.1080/1061186X.2025.2456929","DOIUrl":"10.1080/1061186X.2025.2456929","url":null,"abstract":"The purpose of this work was to create and assess Lornoxicam (LOR) loaded Novasomes (Novas) for the efficient treatment of ulcerative colitis. The study was performed using a 23 factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: Surface Active agent (SAA) type (X1), LOR concentration (X2), and SAA: Oleic acid ratio (X3). The dependent responses included encapsulation efficiency (Y1: EE %), particle size (Y2: PS), zeta potential (Y3: ZP), and polydispersity index (Y4: PDI). The vesicles demonstrated remarkable LOR encapsulation efficiency, ranging from 81.32 ± 3.24 to 98.64 ± 0.99%. The vesicle sizes ranged from 329 ± 9.88 to 583.4 ± 9.04 nm with high negative zeta potential values. The release pattern for Novas' LOR was biphasic and adhered to Higuchi's model. An in-vivo study assessed how LOR-Novas affected rats' acetic acid-induced ulcerative colitis (UC). The optimised LOR-Novas effectively reduced colonic ulceration (p < 0.05) and reduced the inflammatory pathway via inhibiting Toll-like receptor 4 (TLR4), Nuclear factor kappa β (NF-κβ) and inducible nitric oxide (iNO). At the same time, it elevated Silent information regulator-1(SIRT-1) and reduced glutathione (GSH) colon contents. Thus, the current study suggested that the formulation of LOR-Novas may be a viable treatment for ulcerative colitis.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"975-988"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006351","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. 抗gpc3抗体和细胞穿透肽CPP44双配体修饰脂质体靶向递送三氧化二砷治疗肝癌。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub 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":"1004-1013"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","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

Niosomes as a targeted drug delivery system in the treatment of breast cancer: preparation, classification and mechanisms of cellular uptake. 乳小体作为治疗乳腺癌的靶向药物传递系统：制备、分类和细胞摄取机制。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-03-03 DOI: 10.1080/1061186X.2025.2468750

Muneeb Ur Rahman, Hafiz Rashid Hussain, Habiba Akram, Muhammad Sarfraz, Muhammad Nouman, Jawad Akbar Khan, Memona Ishtiaq

{"title":"Niosomes as a targeted drug delivery system in the treatment of breast cancer: preparation, classification and mechanisms of cellular uptake.","authors":"Muneeb Ur Rahman, Hafiz Rashid Hussain, Habiba Akram, Muhammad Sarfraz, Muhammad Nouman, Jawad Akbar Khan, Memona Ishtiaq","doi":"10.1080/1061186X.2025.2468750","DOIUrl":"10.1080/1061186X.2025.2468750","url":null,"abstract":"Breast cancer (BC) remains one of the significant health issues across the globe, being diagnosed in millions of women worldwide annually. Conventional therapeutic options have substantial adverse effects due to their non-specificity and limited drug bioavailability. Niosomes, being novel drug delivery systems formed from non-ionic surfactants, with or without cholesterol and charge-inducing agents, are used as therapeutic options in treating BC. Their formulation by various methods enhances the therapeutic efficacy and bioavailability and minimises side effects. Niosomal formulation of tamoxifen exhibits target drug delivery with enhanced stability, whereas docetaxel and methotrexate show sustained and controlled drug release, respectively. 5-Fluorouracil, doxorubicin, paclitaxel, cyclophosphamide and epirubicin show improved cytotoxic effects against BC when combined with other agents. Furthermore, repurposed niosomal formulations of anti-cancer drugs show improved penetration, reduced tumour volume and significantly enhanced anti-tumour effect. This review article focuses on the composition of niosomes and their application in BC treatment and then examines how niosomes could contribute to BC research.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"916-932"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441122","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

Epidermal growth factor receptors unveiled: a comprehensive survey on mutations, clinical insights of global inhibitors, and emergence of heterocyclic derivatives as EGFR inhibitors. 表皮生长因子受体揭幕：对突变的全面调查，全球抑制剂的临床见解，以及作为EGFR抑制剂的杂环衍生物的出现。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-01 Epub Date: 2025-01-13 DOI: 10.1080/1061186X.2024.2449495

Manojmouli C, T Y Pasha, Mohamed Rahamathulla, Gagana H P, Kavya B L, Gagana K M, Purushotham K N, Shalam M Hussain, Mohammed Muqtader Ahmed, Thippeswamy Boreddy Shivanandappa, Ismail Pasha

{"title":"Epidermal growth factor receptors unveiled: a comprehensive survey on mutations, clinical insights of global inhibitors, and emergence of heterocyclic derivatives as EGFR inhibitors.","authors":"Manojmouli C, T Y Pasha, Mohamed Rahamathulla, Gagana H P, Kavya B L, Gagana K M, Purushotham K N, Shalam M Hussain, Mohammed Muqtader Ahmed, Thippeswamy Boreddy Shivanandappa, Ismail Pasha","doi":"10.1080/1061186X.2024.2449495","DOIUrl":"10.1080/1061186X.2024.2449495","url":null,"abstract":"Mutations that overexpress the epidermal growth factor receptor (EGFR) are linked to cancers like breast (15-20%), head and neck (10-15%), colorectal (5-8%), and non-small cell lung cancer (10-50%), especially in East Asian populations. EGFR activation stimulates 'RAS/RAF/MEK/ERK, PI3K/Akt, and MAPK' pathways, which enhance cell division, survival, angiogenesis, and tumour growth while inhibiting apoptosis and metastasis. Secondary mutations (e.g. 'T790M', 'C797S'), off-target effects, and resistance due to alternate pathway activation reduce the efficacy of currently available EGFR inhibitors. To address these issues, 'novel heterocyclic inhibitors with structural versatility were developed to improve selectivity and binding affinity for mutant EGFR forms'. These new EGFR reduce side effects, enhance pharmacokinetics, and enhance therapeutic efficacy at low concentrations. This review focuses on 'EGFR mutations in various cancers' detailing the biochemical effects, clinical profiles, and binding interactions of globally approved EGFR inhibitors. Furthermore, it focuses into recent progress in nano-formulations and the development of heterocyclic derivatives that can successfully 'target mutant EGFRs' through varied synthesis methods. These inhibitors have the potential to have better binding affinities, selectivity's, and less side-effect. Further research required to refine the structures and develop nanoformulations of EGFR-targeted therapeutics in order to improve therapeutic efficiency and, provide more effective cancer treatments.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"933-951"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931993","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