Department of Pharmacy, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
School of Materials Science and Engineering, College of Engineering, Nanyang Technological University, Singapore 639798, Republic of Singapore.
Mol Med Rep. 2019 Jan;19(1):490-498. doi: 10.3892/mmr.2018.9689. Epub 2018 Nov 23.
The present study investigated the feasibility of improving the tumor‑targeting efficacy and decreasing the toxicity of liposomal cabazitaxel (Cab) with aptamer modification. The process involved preparing aptamer (TLS1c)‑modified liposomes and studying the behavior of the liposomes in vitro and in vivo. TLS1c as an aptamer, which has high specificity for BNL 1ME A.7R.1 (MEAR) cells, was conjugated with Cab liposomes (Cab/lipo) to enhance MEAR tumor tissue targeting. Confocal laser scanning microscopy and flow cytometry analyses demonstrated that the fluorescence of the liposomes modified with the aptamer was notably stronger compared with that of the unmodified liposomes. Furthermore, the biodistribution data of the modified liposomes tested in tumor‑bearing mice revealed high specificity of biotinylated TLS1c‑modified Cab/lipo (BioTL‑Cab/lipo) for tumor tissues. Furthermore, the modified liposomes demonstrated decreased cytotoxicity and simultaneously retained potent inhibition against tumor growth. It is likely that the specific binding of the aptamer (TLS1c) to the targeted cells (MEAR) facilitates the binding of the liposomes to the targeted cells. Therefore, BioTL‑Cab/lipo may be considered as a promising delivery system to improve cell targeting and reduce drug toxicity in the treatment of cancer.
本研究旨在探讨通过适配体修饰提高脂质体多西他赛(Cab)的肿瘤靶向效率并降低其毒性的可行性。该过程包括制备适配体(TLS1c)修饰的脂质体,并研究其在体外和体内的行为。TLS1c 作为一种适配体,对 BNL 1ME A.7R.1(MEAR)细胞具有高度特异性,与 Cab 脂质体(Cab/lipo)缀合,以增强 MEAR 肿瘤组织靶向性。激光共聚焦扫描显微镜和流式细胞术分析表明,与未修饰的脂质体相比,修饰后的脂质体的荧光明显增强。此外,在荷瘤小鼠中测试修饰后的脂质体的生物分布数据表明,生物素化的 TLS1c 修饰的 Cab/lipo(BioTL-Cab/lipo)对肿瘤组织具有高度特异性。此外,修饰后的脂质体显示出降低的细胞毒性,同时保留对肿瘤生长的有效抑制作用。可能是适配体(TLS1c)与靶细胞(MEAR)的特异性结合促进了脂质体与靶细胞的结合。因此,BioTL-Cab/lipo 可以被认为是一种有前途的递药系统,以提高细胞靶向性并降低癌症治疗中的药物毒性。