School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
AAPS PharmSciTech. 2020 Apr 27;21(4):124. doi: 10.1208/s12249-020-01655-7.
To achieve improved drug delivery efficiency to hepatocellular carcinoma (HCC), biodegradable poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP), surface-modified with SP94 peptide, were designed for the efficient delivery of cryptotanshinone to the tumor for the treatment of HCC. Cryptotanshinone NP and SP94-NP were prepared by using nanoprecipitation. The physicochemical and pharmaceutical properties of the NP and SP94-NP were characterized, and the release kinetics suggested that both NP and SP94-NP provided continuous, slow release of cryptotanshinone for 48 h. The in vitro cellular experiment demonstrated that SP94-NP significantly enhanced the cellular uptake of cryptotanshinone and induced high cytotoxicity and cellular apoptosis of hepatocellular carcinoma (HepG2) cells. The in vivo detecting results of targeting effect using the Cy5.5 probe evidenced that SP94-NP showed an accumulation in tumor more efficiently than that of unconjugated ones. Meanwhile, SP94-NP exhibited the smallest tumor size than other groups and showed no toxicity to body. The results of this study provide a promising nanoplatform for the targeting of HCC.
为了提高对肝细胞癌 (HCC) 的药物递送效率,设计了表面修饰有 SP94 肽的可生物降解的聚乙二醇-聚(乳酸-共-羟基乙酸)(PEG-PLGA)纳米粒子 (NP),用于将 cryptotanshinone 有效递送至肿瘤以治疗 HCC。通过纳米沉淀法制备了 cryptotanshinone NP 和 SP94-NP。对 NP 和 SP94-NP 的理化和药物特性进行了表征,释放动力学表明 NP 和 SP94-NP 均能在 48 h 内持续缓慢释放 cryptotanshinone。体外细胞实验表明,SP94-NP 显著增强了 cryptotanshinone 的细胞摄取,并诱导肝癌 (HepG2) 细胞产生高细胞毒性和细胞凋亡。使用 Cy5.5 探针进行的靶向效果的体内检测结果表明,SP94-NP 在肿瘤中的积累效率明显高于未缀合的探针。同时,SP94-NP 表现出最小的肿瘤尺寸,并且对身体没有毒性。这项研究的结果为 HCC 的靶向治疗提供了一个有前途的纳米平台。