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叶酸包裹的硝普银纳米颗粒用于卵巢癌的靶向治疗

Folic acid encapsulated silver nitroprusside nanoparticles for targeted therapy in ovarian cancer.

作者信息

Patel Arti, Londhe Swapnali, Tripathy Sanchita, Nagchowdhury Proma, Patra Chitta Ranjan

机构信息

Applied biology , Indian Institute of Chemical Technology CSIR, Uppal Road, Tarnaka, Hyderabad 500007, AP, Hyderabad, 500007, INDIA.

Applied Biology, CSIR - Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007, INDIA.

出版信息

Biomed Mater. 2025 Apr 30. doi: 10.1088/1748-605X/add2b9.

Abstract

Ovarian cancer is the most prevalent fatal, gynecological malignancy in women, resulting poor survival rate (5th in cancer deaths) owing to its asymptomatic nature. The unmet medical challenges for ovarian cancer are associated with several limitations such as poor bioavailability, non-specificity and toxicity related issues. Targeted drug delivery systems may over come the existing limitations. Utilizing the concept of overexpression of folate receptors in the ovarian carcinoma, in the present study, we have designed folate receptor targeted drug delivery system(AgNNPs-FA) by the combination of silver nitroprusside nanoparticles (AgNNPs) because of its inherant anti-cancer property as established by our group and folic acid (FA) as targeting agent that target folate receptors. Initially, both and AgNNPs and AgNNPs-FA were designed and later characterized using several analytical tools such as DLS, XRD, SEM, TEM,TGA,HPLC and FTIR etc. The in vitro cell viability assay in CHO cell line suggests the biocompatible nature of AgNNPs-FA. The targeted anticancer activity of the AgNNPs-FA is established in human ovarian adenocarcinoma (SK-OV-3) through several in vitro assays and compared with AgNNPs. All in vitro assays (cell viability assay, thymidine incorporation assay, scratch assay, cell cycle, apoptosis assay, tunnel assay) in SK-OV-3 and in vivo experiment (CAM assay) in fertilized eggs with AgNNPs-FA shows more anti-cancer activity in targeted fashion than that of AgNNPs. The plausible mechanisms behind the anti-cancer activity of the nanoparticles were demonstrated through ROS assay (DCFDA and DHE staining), JC-1 staining, immunocytochemistry staining (Ki-67) and Western blot analysis. The results altogether support that these targeted drug delivery system could be used as an alternative treatment strategy for ovarian cancer and other cancer having overexpression of folate receptors.

摘要

卵巢癌是女性中最常见的致命妇科恶性肿瘤,因其无症状的特性导致生存率较低(在癌症死亡原因中排第五)。卵巢癌尚未满足的医学挑战与生物利用度低、非特异性和毒性相关问题等多种局限性有关。靶向给药系统可能会克服现有局限性。利用卵巢癌中叶酸受体过表达的概念,在本研究中,我们通过将硝普银纳米颗粒(AgNNPs)与叶酸(FA)相结合,设计了叶酸受体靶向给药系统(AgNNPs-FA),其中AgNNPs因其固有的抗癌特性已由我们的团队证实,FA作为靶向剂靶向叶酸受体。最初,设计了AgNNPs和AgNNPs-FA,随后使用动态光散射(DLS)、X射线衍射(XRD)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、热重分析(TGA)、高效液相色谱(HPLC)和傅里叶变换红外光谱(FTIR)等多种分析工具对其进行表征。在CHO细胞系中进行的体外细胞活力测定表明了AgNNPs-FA的生物相容性。通过多种体外试验在人卵巢腺癌(SK-OV-3)中确立了AgNNPs-FA的靶向抗癌活性,并与AgNNPs进行了比较。在SK-OV-3中进行的所有体外试验(细胞活力测定、胸苷掺入试验、划痕试验、细胞周期、凋亡试验、隧道试验)以及在受精卵中使用AgNNPs-FA进行的体内实验(鸡胚绒毛尿囊膜试验)均显示,与AgNNPs相比,AgNNPs-FA以靶向方式表现出更强的抗癌活性。通过活性氧(ROS)测定(2',7'-二氯二氢荧光素二乙酸酯(DCFDA)和二氢乙锭(DHE)染色)、JC-1染色、免疫细胞化学染色(Ki-67)和蛋白质印迹分析证明了纳米颗粒抗癌活性背后的可能机制。这些结果共同支持,这些靶向给药系统可作为卵巢癌和其他具有叶酸受体过表达的癌症的替代治疗策略。

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