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叶酸靶向治疗性立方脂质体平台的合成用于体外和体内共递送氧化铋和阿霉素治疗黑色素瘤。

Synthesis of folate targeted theranostic cubosomal platform for co-delivery of bismuth oxide and doxorubicin to melanoma in vitro and in vivo.

机构信息

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Eur J Pharm Biopharm. 2024 May;198:114259. doi: 10.1016/j.ejpb.2024.114259. Epub 2024 Mar 12.

Abstract

Liquid crystalline nanoparticles (LCNPs) have gained much attention in cancer nanomedicines due to their unique features such as high surface area, storage stability, and sustained-release profile. In the current study, a novel LCNP for co-encapsulation of BiO and hydrophilic doxorubicin (DOX) was fabricated and functionalized with folic acid (FA) to achieve efficient tumor targeting toward CT-scan imaging and chemotherapy of melanoma in vitro and in vivo. LCNPs BiO NPs were prepared using glycerol monooleate-pluronic F-127 (GMO/PF127/water). Firstly, GMO/water were homogenized to prepare LC gel. Then, the stabilizer aqueous solution (PF127/BiO/DOX) was added to the prepared LC gel and homogenized using homogenization and ultrasonication. The formulated NPs exhibited superior stability with encapsulation efficiency. High cytotoxicity and cellular internalization of the FA-BiO-DOX-NPs were observed in comparison with BiO-DOX-NPs and the free DOX in folate-receptor (FR) overexpressing cells (BF) in vitro. Moreover, ideal tumor suppression with increased survival rate were observed in tumorized mice treated with FA-BiO-DOX-NPs compared to those treated with non-targeted one. On the other hand, the CT-imaging ability of the BiO-DOX-NPs was tested inBF tumor-bearing mice. The obtained data indicated a high potential of the developed targeted theranostic FA-BiO-DOX-NPs for diagnostics and treatment of melanoma.

摘要

液晶纳米颗粒 (LCNPs) 因其具有高比表面积、储存稳定性和持续释放等独特特性,在癌症纳米医学中受到了广泛关注。在本研究中,制备了一种新型 LCNP,用于共包封 BiO 和亲水性阿霉素 (DOX),并通过叶酸 (FA) 进行功能化,以实现对黑色素瘤的 CT 成像和体外及体内化疗的高效肿瘤靶向。LCNPs BiO NPs 是使用甘油单油酸酯-泊洛沙姆 F-127 (GMO/PF127/水) 制备的。首先,将 GMO/水均质制备 LC 凝胶。然后,将稳定剂水溶液 (PF127/BiO/DOX) 添加到制备的 LC 凝胶中,并通过匀浆和超声处理进行均质化。与 BiO-DOX-NPs 和游离 DOX 相比,所制备的 NPs 表现出优异的稳定性和包封效率。在 FR 过表达细胞 (BF) 中,FA-BiO-DOX-NPs 表现出更高的细胞毒性和细胞内吞作用。此外,与非靶向组相比,荷瘤小鼠用 FA-BiO-DOX-NPs 治疗后观察到理想的肿瘤抑制和生存率提高。另一方面,在 BF 荷瘤小鼠中测试了 BiO-DOX-NPs 的 CT 成像能力。获得的数据表明,开发的靶向治疗性 FA-BiO-DOX-NPs 具有用于黑色素瘤诊断和治疗的高潜力。

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