Dual-Modified Novel Biomimetic Nanocarriers Improve Targeting and Therapeutic Efficacy in Glioma.

Abstract

Glioma is a fatal disease with limited treatment options and very short survival. Although chemotherapy is one of the most important strategies in glioma treatment, it remains extremely clinically challenging largely due to the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Thus, the development of nanoparticles with both BBB and BBTB penetrability, as well as glioma-targeting feature, is extremely important for the therapy of glioma. New findings in nanomedicine are promoting the development of novel biomaterials. Herein, we designed a red blood cell membrane-coated solid lipid nanoparticle (RBCSLN)-based nanocarrier dual-modified with T7 and NGR peptide (T7/NGR-RBCSLNs) to accomplish these objectives. As a new kind of biomimetic nanovessels, RBCSLNs preserve the complex biological functions of natural cell membranes while possessing physicochemical properties that are needed for efficient drug delivery. T7 is a ligand of transferrin receptors with seven peptides that is able to circumvent the BBB and target to glioma. NGR is a peptide ligand of CD13 that is overexpressed during angiogenesis, representing an excellent glioma-homing property. After encapsulating vinca alkaloid vincristine as the model drug, T7/NGR-RBCSLNs exhibited the most favorable antiglioma effects in vitro and in vivo by combining the dual-targeting delivery effect. The results demonstrate that dual-modified biomimetic nanoparticles provide a potential method to improve drug delivery to the brain, hence increasing glioma therapy efficacy.