Liu Hui-Qin, Wu Xi-Dong, Fang Xue-Wen, An Yun-Song, Xia Meng, Luo Xiao-Hua, Li Jun-Zheng, Wang Guan-Hai, Liu Tao
Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
Shantou University Medical College, Shantou, Guangdong 515063, China.
ACS Omega. 2024 Dec 9;9(50):49566-49579. doi: 10.1021/acsomega.4c07132. eCollection 2024 Dec 17.
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. Unfortunately, current treatments encounter multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), resulting in the efflux of chemotherapy drugs, is one of the significant mechanisms causing MDR. d-α-Tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) has been demonstrated to effectively inhibit P-gp expression. The objectives of this study are to improve tumor MRI imaging, optimize docetaxel (DOC) administration, and target P-gp to overcome NPC resistance. Multifunctional micelles of TPGS (MM@DOC), loaded with magnetic nanoparticles, were synthesized for the targeted delivery of the first-line anticancer drug. MM@DOC exhibited greater toxicity and induced higher levels of apoptosis in DOC-resistant NPC cells (C666-1/DOC) compared to DOC. MM@DOC loaded with magnetic nanoparticles improved the quality of tumor MRI imaging. MM@DOC also demonstrated significant antitumor effects in nude mice with C666-1/DOC NPC. In conclusion, MM@DOC exhibited promising inhibitory effects on resistant tumors both in vitro and in vivo, optimized tumor MRI imaging, and showed great potential in drug delivery and overcoming resistance.
鼻咽癌(NPC)在中国南方地区较为常见。不幸的是,目前的治疗方法面临多药耐药(MDR)问题。P-糖蛋白(P-gp)的过表达导致化疗药物外排,是引起MDR的重要机制之一。聚乙二醇1000琥珀酸酯维生素E(TPGS)已被证明能有效抑制P-gp的表达。本研究的目的是改善肿瘤磁共振成像(MRI)、优化多西他赛(DOC)给药方式并靶向P-gp以克服鼻咽癌耐药性。合成了负载磁性纳米颗粒的TPGS多功能胶束(MM@DOC)用于一线抗癌药物的靶向递送。与DOC相比,MM@DOC对多西他赛耐药的鼻咽癌细胞(C666-1/DOC)表现出更大的毒性并诱导更高水平的细胞凋亡。负载磁性纳米颗粒的MM@DOC改善了肿瘤MRI成像质量。MM@DOC在携带C666-1/DOC鼻咽癌的裸鼠中也显示出显著的抗肿瘤作用。总之,MM@DOC在体外和体内对耐药肿瘤均表现出有前景的抑制作用,优化了肿瘤MRI成像,在药物递送和克服耐药性方面显示出巨大潜力。