Cancer cell targeting and therapeutic delivery of silver nanoparticles by mesoporous silica nanocarriers: insights into the action mechanisms by quantitative proteomics

Abstract

The aim of the present work is to provide an approach to safely deliver silver nanoparticles (AgNPs) as cytotoxic agents into cancer cells, and to provide a deeper insight into the cellular mechanisms affected by such targeted delivery. The use of mesoporous silica nanoparticles (MSNs) as nanovehicles decorated with transferrin (Tf, targeting agent) provides a nanoplatform for the nucleation and immobilization of AgNPs (MSNs-Tf-AgNPs). We have performed the physico-chemical characterization of the nanosystems and evaluated their therapeutic potential using bioanalytical strategies to estimate the efficiency of the targeting, the degree of cellular internalization in two cell lines with different TfR expression, and the cytotoxic effects of the delivered AgNPs. In addition, cellular localization of the nanosystems in cells has been evaluated by a transmission electron microscopy analysis of ultrathin sections of Human hepatocarcinoma (HepG2) cells exposed to MSNs-Tf-AgNPs. The in vitro assays demonstrate that only the nanosystem functionalized with Tf is able to transport the AgNPs inside the cells which overexpress transferrin receptors. Therefore, this novel nanosystem is able to deliver AgNPs specifically to cancer cells overexpressing Tf receptors and offers the possibility of a targeted therapy using reduced doses of silver nanoparticles as cytotoxic agents. Then, a quantitative proteomic experiment validated through the analysis of gene expression has been performed to identify the action molecular mechanisms associated with the chemotherapeutic potential of the MSNs-Tf-AgNPs nanocarriers.