Lactobionic acid-decorated TPGS nanoparticles to decrease multidrug resistance on hepatocellular carcinoma
- VernacularTitle:Элэгний эсийн хавдрын үеийн эмэнд тэсвэржилтийг лактобионы хүчил холбоот ТПГС нанопартиклиар бууруулах нь
- Author:
Altansukh Ts
1
;
Jing Yao
2
;
Jianping Zhou
2
Author Information
1. Mongolian National University of Medical Sciences
2. China Pharmaceutical University
- Publication Type:Journal Article
- Keywords:
TPGS-LA conjugate;
Hepatocellular carcinoma;
Multidrug resistance;
Etoposide
- From:
Mongolian Pharmacy and Pharmacology
2019;14(1):6-11
- CountryMongolia
- Language:Mongolian
-
Abstract:
Introduction:Many effective anticancer drugs are limited to use for hepatocellular carcinoma
(HCC) therapy due to drug resistance mechanisms in liver cells. In recent years, tumor-targeted
drug delivery and inhibition of drug resistance-related mechanisms become an integrated strategy
to combat effectively chemoresistant cancer.
Aim:Herein, lactobionic acid-conjugated D-α-Tocopheryl polyethylene glycol 1000 succinate
(TPGS-LA conjugate) was developed as a potential asialoglycoprotein receptor (ASG PR (-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO)
efficacy against HCC.
Methods:Main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in
vitro and in vivo studies after prepared using nanoprecipitation method and characterized by dynamic light scattering (DLS).
Results:According to the results, smaller sized (~141.43 nm) and positively charged ETO-loaded
TPGS-LA NPs were more suitable to provide an efficient delivery to hepatoma cells by avoiding
clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs could enhance noticeably
cytotoxicity of ETO in HepG2 cells. Besides, markedly higher internalization by ASGPR overexpressed HepG2 cells and efficient accumulation at tumor site in vivo were revealed in TPGS-LA
NPs group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved
the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to ETO-loaded TPGS NPs.
Conclusion:These results suggest that TPGSLA NPs could be used as a potential delivery system of ETO against HCC.
- Full text:MPPJ-2019-14(1)-6-11.pdf
