RESUMO
Nano-graphene oxide (NGO) has been proposed as a novel drug carrier. However, the poor biocompatibility and physiological stability as well as lack of cancer targeting capability have limited its further applications in cancer therapy. To solve this problem, we developed a novel nanohybrid of NGO/DOX@SPC-FA by first allowing soy phosphatidylcholine membrane (SPC) to encapsulate DOX-loaded NGO (NGO/DOX) and then modifying the SPC membrane with PEGylated lipid-FA conjugate to achieve the display of cancer targeting FA on the nanohybrid surface. The SPC membrane (mimicking cell membrane) enabled the resultant nanohybrids (NGO/DOX@SPC-FA) to exhibit good stability and biocompatibility, high drug loading capability, efficient cellular uptake, and controlled drug release. Moreover, compared with NGO/DOX and SPC-modified NGO/DOX (NGO/DOX@SPC), the FA-modified NGO/DOX@SPC nanohybrids (NGO/DOX@SPC-FA) could deliver NGO/DOX to cancer cells with improved delivery and killing efficacy due to the presence of FA targeting motifs on the surface. The NGO/DOX@SPC-FA nanohybrids were found to be internalized specifically by FA-positive cancer cells (Hela cells) through both macropinocytosis-directed engulfment and clathrin-dependent endocytosis, and then become localized into the lysosomes. In vivo biodistribution study showed that NGO/DOX@SPC-FA had a high tumor targeting ability because of the active targeting mechanism with folate modification. In vivo antitumor therapy study demonstrated NGO/DOX@SPC-FA could significantly inhibit tumour growth and prolong the survival time of mice. Our results suggest that NGO/DOX@SPC-FA, as a novel drug delivery system with high drug loading and targeted delivery efficiency, holds promise for future cancer therapy.
