Preparation and characterization of erythrocyte membrane cloaked PLGA/arsenic trioxide nanoparticles and evaluation of their<i>in vitro</i>anti-tumor effect

Abstract

Arsenic trioxide (ATO) is used for acute promyelocytic leukemia (APL) that is resistant to all-<i>trans</i>-retinoic acid, but its direct intravenous injection sometimes induces severe toxic side effects. Here, we developed a delivery system of red blood cell membrane (RBCM) cloaked poly (lactic-<i>co</i>-glycolic) acid (PLGA)-ATO nanoparticles (RPANs) to reduce the toxicity. PLGA was used to entrap the ATO, and the PLGA-ATO nanoparticles (PANs) were prepared by the emulsification method. Then RBCMs were employed to cloak the PANs using ultrasonication, to develop the RPANs delivery system. The prepared RPANs had a uniform size of around 233.6 nm with an obvious core-shell structure, as observed by TEM. The completeness of the membrane proteins was confirmed by SDS-PAGE and an <i>in vitro</i> release time of 65 h was determined for the RPANs. The RPANs also exhibited low cytotoxicity against the 293k kidney cell line (84.6% cell viability rate), which suggested that the ATO toxicity was reduced by RBCM cloaking. Moreover, the anti-tumor effects of the RPANs against the HL60 cell line were comparable to those of ATO solution. Our study demonstrated that the RPANs system has anti-tumor potential and could be developed into a safe and sustained release delivery system for ATO.