In vivo anti-tumor activity of tumor-targeting pH-sensitive lipoprotein-mimic nanocarrier with paclitaxel loaded / 中国中药杂志

Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.

Anti-Tumor Activity of Tumor-Targeting pH-Sensitive Lipoprotein-Mimic Nanocarrier Loaded with Paclitaxel / 中国药学杂志

OBJECTIVE: To construct a tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel(BSA-LC/DOPE-PTX)for effective antitumor therapy. METHODS: In vitro drug release study was conducted using dialysis method. The stability of BSA-LC/DOPE-PTX was studied by testing the aggregation of BSA-LC/DOPE-PTX in 50% human plasma. The cytotoxicity of drug-loaded nanocarrier against MCF-7 cells was evaluated by standard MTT assay. The subcellular localization and intracellular drug release behavior of BSA-LC/DOPE were evaluated by LSCM. RESULTS: In vitro drug release study demonstrated that paclitaxel(PTX)was released from BSA-LC/DOPE in a pH-dependent manner. The stability study showed that there was no significant change, suggesting that the coupling BSA could increase the stability in plasma. The cellular inhibition of BSA-LC/DOPE-PTX with BSA targeting agents was greater than that of LC/DOPE-PTX. BSA-LC/DOPE facilitated the capacity of endosomal escape, and rapidly released the loaded agents into the cytoplasm under acid conditions in lysosomes. CONCLUSION: BSA-LC/DOPE, as biocompatible, tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier, is a promising system for effective intracellular delivery of PTX to tumors with optimal anti-tumor efficacy.