Folate-decorated and NIR-triggered nanoparticles loaded with platinum(IV)-prodrug plus 5-fluorouracil for targeted and chemo-photothermal combination therapy

Abstract

Cisplatin, although promising in clinical use, is seriously limited by its nonspecific biodistribution and severe side effects. One of the potential strategies to improve the targeted delivery of cisplatin and prolong its circulation is to use platinum(IV) complexes as prodrugs and deliver them with nanocarriers. Here, a novel combinatorial drug delivery system loaded with Pt(IV)-prodrug plus 5-FU for targeted and chemo-photothermal therapy of folate receptor-positive ovarian cancer cells was developed. By doping with indocyanine green (ICG), the drug-loaded nanoparticles (abbreviated as Pt(IV)-FU-FINPs) had about 130 nm spherical structure which was comprised of a poly(lactide-co-glycolic acid) (PLGA) core, a composite layer of soybean lecithin mixed with PEGylated phospholipid, and a folate-targeted ligand to actively recognize tumors. Compared with free ICG and folate-absent nanoparticles, Pt(IV)-FU-FINPs with near-infrared (NIR) laser irradiation exhibited photo-responsive drug release behavior and promoted folate receptor-mediated cellular endocytosis. In addition, in vitro cytotoxicity assay demonstrated that the cytotoxic effect of Pt(IV)-FU-FINPs with NIR laser irradiation was a little lower than that of free cisplatin plus free 5-FU, but higher than that of free cisplatin or Pt(IV)-FU-FINPs without laser treatment. Hence, this co-delivery system appears to be a promising platform for targeted and chemo-photothermal therapy of ovarian cancer.