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

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 tumour barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability, as well as glioma-targeting ability, is of great importance for glioma therapy. New frontiers in nanomedicine are advancing the research of novel biomaterials. Herein, we constructed a red blood cell membrane-coated solid lipid nanoparticle (RBCSLN)-based drug delivery system with dual-modification of the T7 and NGR peptide ligand (T7/NGR-RBCSLNs) to achieve these goals. As a new class of biomimetic nanoparticles, RBCSLNs retain the complex biological functions of natural cell membranes while exhibiting physicochemical properties that are suitable for effective drug delivery. T7 is a seven-peptide ligand of transferrin receptors (TfR) that is capable of circumventing the BBB and targeting glioma. NGR is a peptide ligand of CD13 that is overexpressed during angiogenesis, representing an excellent glioma-homing property. After encapsulating vinca alkaloid vincristine (VCR) as the model drug, T7/NGR-RBCSLNs exhibited the most favourable antiglioma effects in vitro and in vivo by combining the dual-targeting delivery effect. These results demonstrate that dual-targeting biomimetic nanocarriers provide a potential method for improving both drug delivery to the brain and glioma treatment efficacy.