Tailored mesoporous silica nanosystem with enhanced permeability of the blood–brain barrier to antagonize glioblastoma

Abstract

Herein, a tailored MSNs nanosystem modified by an RGD peptide has been rationally designed, synthesized and used as a carrier of anticancer agents to enhance its BBB permeability and anticancer efficacy to treat human brain glioma.

Abstract

Cancer-targeted drug delivery systems with permeability of the blood–brain barrier (BBB) have become of great interest for the rational design of high-efficiency anticancer agents. Herein, a tailored mesoporous silica nanoparticles (MSNs) nanosystem modified by RGD (arginine–glycine–aspartate) peptide was designed and tested for use as a carrier of anticancer agents, by using a novel organic selenium compound BSeC as a model molecule. As expected, the nanosystem (BSeC@MSNs-RGD) could effectively enhance the BBB permeability and the cellular uptake of BSeC in tumor cells. The internalized BSeC@MSNs-RGD triggered mitochondrial dysfunction and intracellular ROS overproduction, which subsequently activated the p53 and MAPKs pathways. Moreover, the nanosystem could inhibit the U87 tumor spheroids growth, significantly prolong the blood circulation time of the loaded drug in vivo and effectively reduce its in vivo toxicity. Taken together, this study provides a strategy for the rational design of a tailored nanomedicine with enhanced BBB permeability to treat human brain glioma.