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 

机构地区：[1]Department of Pharmaceutics,Key Laboratory of Chemical Biology(Ministry of Education),School of Pharmaceutical Sciences,Shandong University,Jinan 250012,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第2期192-202,共11页亚洲药物制剂科学（英文）

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).

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 delivery.CBP/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent evaporation.They exhibited vesicle-like spherical morphology,uniform particle size and negative zeta potential.Reaching 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 site.After 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 solution.After internalized by RM-1 cells,the gas-blasting release process was tested in acid environment.It was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting release.In vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P<0.05).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 cytoplasm.Furthermore,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus delivery.And 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 solution.At last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer therapy.CBP/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study.All of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment.

关 键 词：CARBOPLATIN NANOCAPSULE pH-responsive release Gas-blasting Prostate cancer 

分 类 号：R737.25[医药卫生—肿瘤] R943[医药卫生—临床医学]