The reversal of multidrug resistance in ovarian carcinoma cells by co-application of tariquidar and paclitaxel in transferrin-targeted polymeric micelles.
In this study, a transferrin (Tf)-modified polyethylene glycol-phosphatidyl ethanolamine (PEG-PE)-based micellar delivery system containing paclitaxel (PTX) and tariquidar (TRQ), a potent third generation P-gp inhibitor, was prepared. The nanoformulation was evaluated by targeting efficiency, cellular association, cellular internalization pathway and cytotoxicity for reversal of PTX resistance on two multidrug resistant (MDR) ovarian carcinoma cell lines, SKOV-3TR and A2780-Adr. PTX and TRQ are both hydrophobic compounds. They were successfully encapsulated into the micellar structure containing vitamin E as the encapsulation enhancer. The Tf-targeted micelles were internalized mainly via clathrin-dependent endocytosis by both cell lines. For SKOV-3TR, additional mechanisms including caveolin-dependent endocytosis and macropinocytosis were found to play a significant role. The PTX cytotoxicity against the SKOV-3TR and A2780-Adr MDR cells was increased significantly in the presence of micellar encapsulation. However, unlike the A2780-Adr cell line, the Tf-targeting effect was significant on SKOV-3TR cells when co-administrated with TRQ. Penetration of the Tf-targeted micelles in a cancer cell spheroid culture was also investigated.
a Xiangya Hospital, Central South University , Changsha , Hunan , China.
Wanting
W
Zou
b Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston , MA , USA.
Can
C
Sarisozen
b Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University , Boston , MA , USA.|c Department of Biochemistry, Faculty of Science , King Abdulaziz University , Jeddah , Saudi Arabia.
Vladimir P
VP
Torchilin
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D005260:Female; D006801:Humans; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011108:Polymers / Q000737:chemistry; D011804:Quinolines / Q000008:administration & dosage
D008823:Micelles; D011108:Polymers; D011804:Quinolines; C402343:tariquidar; D017239:Paclitaxel
Co-delivery; P-glycoprotein; micelles; multidrug resistance; targeted drug delivery; transferrin