Synthesis of calcium phosphate/GPC-mPEG hybrid porous nanospheres for drug delivery to overcome multidrug resistance in human breast cancer

Abstract

Calcium phosphate/glycerylphosphorylcholine (GPC)-mPEG hybrid porous nanospheres (CaP/GPC-mPEG NSs) were prepared by a facile room-temperature method and employed as carriers to deliver mitoxantrone (MIT) as well as to overcome multidrug resistance (MDR). The successful synthesis of CaP/GPC-mPEG NSs was determined by FTIR and ¹H-NMR. The MIT encapsulating efficiency of the NSs was 89.5 wt% with a loading content of 6.0 wt%. The release of MIT at neutral pH was fast, with close to 76% of its total drug content being released within the first 24 h. The as-prepared CaP/GPC-mPEG NSs were quite safe as confirmed by MTT assays. The cytotoxicities and cellular uptake of drug-loaded CaP/GPC-mPEG NSs were tested against human breast cancer (MCF-7) cells and their multidrug resistant (MCF-7/MIT) cells. Compared to free MIT, the MIT-loaded CaP/GPC-mPEG NSs exhibited high cytotoxicities in MCF-7 and MCF-7/MIT cells. The results suggest that CaP/GPC-mPEG NSs greatly enhanced the cellular uptake efficiency, and this was supported by confocal laser scanning microscopy. Additionally, both CaP and GPC-mPEG are biocompatible and biodegradable thus the as-prepared CaP/GPC-mPEG hybrid porous nanospheres are promising for drug delivery and overcoming MDR.