Preparation of mitochondrial targeted calcium arsenite/doxorubicin lipid nanoparticles and the in vitro study in reversing tumor drug resistance
10.16438/j.0513-4870.2021-1169
- VernacularTitle:线粒体靶向亚砷酸钙/多柔比星脂质纳米粒的制备及其逆转肿瘤耐药性的体外研究
- Author:
Ke ZHANG
1
;
Tian-xiang YUE
1
;
Meng-ying CHENG
1
;
Zeng-ying LIANG
1
;
Ji-gang PIAO
1
,
2
;
Hong-yue ZHENG
3
;
Heng-wu XU
4
;
Fan-zhu LI
1
,
2
Author Information
1. College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China
2. Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, Hangzhou 310000, China
3. Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou 310000, China
4. Department of Pharmacy, Jinhua People's Hospital, Jinhua 321000, China
- Publication Type:Research Article
- Keywords:
neoplasm;
mitochondria;
arsenic trioxide;
lipid nanoparticle;
rug resistance
- From:
Acta Pharmaceutica Sinica
2021;56(12):3243-3251
- CountryChina
- Language:Chinese
-
Abstract:
This study aims at the critical role of P-glycoprotein (P-gp) in tumor drug resistance, taking advantage of the adenosine triphosphate (ATP) dependence of P-gp mediated drug transport and efflux across the cell membrane. Mitochondrial targeted calcium arsenite/doxorubicin (DOX) lipid nanoparticles were constructed via hydrothermal method and thin-film dispersion method for reversing tumor drug resistance. The results showed that the lipid nanoparticles were uniform in size and well dispersed with a mean particle size of (261 ± 7) nm, zeta potential of (-9.6 ± 1.3) mV. The DOX loading efficiency and encapsulation efficiency were 22.6% and 84.0%. The in vitro drug release profile was pH-dependent; the drug accumulation at mitochondria was significantly increased, which then caused overload of calcium and inhibition of P-gp and ATP, thereby reversing tumor drug resistance. The simultaneously released arsenite ion and DOX could synergistically kill the tumor cells. In summary, the lipid nanoparticles prepared in this study have uniform particle size, high drug loading efficiency and encapsulation efficiency, excellent colloidal stability, pH responsiveness, and impressive ability to reverse tumor drug resistance, which may hold great potential in further clinical applications.
