Synthesis of nanocarriers with remote magnetic drug release control and enhanced drug delivery for intracellular targeting of cancer cells

Abstract

Nanotherapeutic strategy is well recognized as the therapeutic approach of the future. Numerous reports have demonstrated the use of nanoparticulate drug carriers for the development of targeted nanotherapeutics by, for instance, incorporation of a moiety that specifically targets certain diseased cells. However, systematic investigation of this aspect has been inadequate, especially with regard to nanosystems with remotely controlled drug delivery. The authors previously designed a magnetic-responsive core–shell drug delivery nanosystem which proved to be technically feasible in vitro. In the present study, this nanosystem is modified for targeted delivery of an anticancer agent (encapsulated camptothecin (CPT)) to cancer cells overexpressing epithelial growth factor receptor (EGFR) with accurate intracellular drug release. The endocytosis of the nanocarriers by cancer cells, the pathway of cellular uptake and the subsequent intracellular controlled drug delivery were systematically investigated. It was found that the modified nanocarriers showed reasonably high drug load efficiency for CPT and a high uptake rate by cancer cells overexpressing EGFR through clathrin-mediated endocytosis. The intracellular release of the CPT molecules via an external magnetic stimulus proved to be technically successful and ensured much higher therapeutic efficacy than that obtained with the free drug. This study employs multiple functions for nanotherapeutic treatment of specific target cells, i.e. cell-specific targeting, controlled cellular endocytosis and magnetic-responsive intracellular drug release.