A convergent fabrication of programmed pH/reduction-responsive nanoparticles for efficient dual anticancer drugs delivery for ovarian cancer treatment

Abstract

A nanoparticle-based drug delivery technology could develop combination cancer therapy more effectively. However, because of inadequate drug delivery into tumor cells, the cancer therapeutic efficiency of nanomedicines is diminished. PEGylated poly(α-lipoic acid) copolymers with (mPEG-PLA) were fabricated and used as pH/reductive responsive nanovesicles to administer Gefitinib (GFT) and doxorubicin (DOX) for the treatment of ovarian cancer. The amphiphilic polymers mPEG-PLA may be efficiently incorporated on DOX and GFT to fabricate DOX and GFT coloaded nanoparticles (DOX@GFT-NPs) and self-assembled into an aqueous solution. The DOX@GFT-NPs released more DOX and GFT after being prepared to respond to pH and reduction stimuli. The outcomes of confocal laser scanning microscopy and flow cytometry findings, the SKOV3 ovarian cancer cells quickly fascinated the dual drugs-coloaded nanoparticles and drugs released intracellularly accumulated. DOX@GFT-NPs triggered cell death and demonstrated synergistic therapeutic benefits in SKOV3 cells. Results showed that the nanoparticles efficiently trigger apoptosis in SKOV3 ovarian cancer cells using morphological staining (acridine orange/ethidium bromide (AO/EB) and HOECHST 33342 nuclear staining). These outcomes show that using pH and reduction stimuli on mPEG-PLA copolymer to treat ovarian cancer is a promising approach.