Gas-blasting nanocapsules to accelerate carboplatin lysosome release and nucleus delivery for prostate cancer treatment

作     者：Shunli Fu Shuang Liang Dandan Jiang Rui Yang Zipeng Zhang Lili Chang Xinke Zhang Yongjun Liu Na Zhang Shunli Fu;Shuang Liang;Dandan Jiang;Rui Yang;Zipeng Zhang;Lili Chang;Xinke Zhang;Yongjun Liu;Na Zhang

作者机构：Department of PharmaceuticsKey Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2021年第16卷第2期

页      面：192-202页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 100214[医学-肿瘤学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：This work was supported by a grant from the National Natural Science Foundation of China(Nos.81773652 and 81974498) the Young Scholar Program of Shandong University(2017WLJH40) 

主　　题：Carboplatin Nanocapsule pH-responsive release Gas-blasting Prostate cancer 

摘      要：To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus ***/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent *** exhibited vesicle-like spherical morphology,uniform particle size and negative zeta *** the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor *** that,the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP *** internalized by RM-1 cells,the gas-blasting release process was tested in acid *** was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting *** vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P0.05).Meanwhile,TEM and the change of the concentration of H+results exhibited that the explosion of CBP/SB 5-NC was more easily happened in lysosome acid environment(pH 5.0).The blasting release can accelerate CBP lysosome release to ***,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus *** the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB 5-NC was higher than CBP *** last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer ***/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological *** of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cance