Enhanced anticancer efficacy of folate-grafted lipid modified dual drug loaded nanoassemblies to reduce drug resistance in ovarian cancer

Abstract

Non-targeted combination chemotherapy is a major clinical challenge for drug resistant ovarian cancer treatment. Lack of the specificity, adverse effect, low survival rate etc limit the chemotherapeutic treatment efficacy of drug resistance cancer. To overcome these obstacles, researchers have focused on nanotechnology based dual targeted therapies, representing a new therapeutic approach, intended to maximize intracellular drug uptake and minimize drug resistance. In this regard, folic acid (FA) conjugated lipid coated mesoporous magnetic nanoassemblies (FA-LMMNA) synthesized for targeted delivery of Doxorubicin and Paclitaxel (DOX:TXL-FA-LMMNA) has been investigated herein. This formulation provides specific targeting effect by folate conjugation, improving the anti-cancer efficacy on cisplatin sensitive and resistant ovarian cancer cells (A2780S and A2780-Cis-Res). DOX:TXL-FA-LMMNA exhibits significant enhancement in anticancer efficacy as compared to dual drug encapsulated lipid modified mesoporous magnetic nanoassemblies (DOX:TXL-LMMNA), which is a non-folate variant. We have observed a significantly higher in vitro cellular uptake and targeting efficacy of DOX:TXL-FA-LMMNA for the A2780S and A2780-Cis-Res (folate receptor positive (FR+ve)) cells due to overexpression of FR on these cell lines. In case of FR negative (FR–ve) prostate cancer (PC3) and normal fibroblast (L929) cells, no significant difference owing to FA was observed. These results suggest that DOX:TXL-FA-LMMNA has the potential activity for targeted delivery of dual drugs for treating cisplatin sensitive and resistant ovarian cancer. The present work promises to overcome the drug resistance and may open up new directions for the targeting combination chemotherapy.