Construction of albumin based nanoparticles utilizing paclitaxel-fatty acid prodrug that mimicking the natural fatty-acid binding process in vivo to synergistically elevate ROS withβ-lapachone for cooperative cancer therapy

Objective The aim of this study was to develop a chemotherapy drug paclitaxel (PTX) and a tumor specific ROS generation agent β-lapachone(LAP) co-loaded human serum albumin (HSA) based nanoparticles (ANPs) for synergistic anticancer therapy.Significance: Albumin based nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. In this study, we mimicked the natural fatty-acid binding process in vivo to construct ANPs to synergistically elevate ROS with β-lapachone for cooperative cancer therapy.Methods: Firstly a polyethylene glycol monostearate(PGM) modified redox-sensitive paclitaxel prodrug(PTX-SS-PGM) was synthesized and stearic acid capable of binding with HSA was introduced. Furtherly, a LAP/PTX-SS-PGM complex was engineered through the π − π stacking interaction and H-bonding between LAP and PTX. The PTX and LAP co-loaded ANPs (PTX-SS-PGM&LAP@HSA) were obtained through the binding between LAP/PTX-SS-PGM complex and HSA.Results: The percentage of apoptosis for PTX, Abraxane®, PTX-SS-PGM@HSA ANPs and PTX-SS-PGM&LAP@HSA ANPs was 8.17%, 9.53%, 15.17% and 28.6%, respectively, demonstrating synergistic cytotoxicity effect. The in vivo imaging test confirmed that PTX-SS-PGM&LAP@HSA had targeting ability to tumor tissues. The obtained ANPs exhibited better tumor growth inhibition in vitro and in vivo.