Enhanced blood–brain barrier penetration and glioma therapy mediated by T7 peptide-modified low-density lipoprotein particles

Abstract

Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature and low permeability of drugs across the blood-brain barrier (BBB). An ideal glioma-targeted delivery system need to traverse the BBB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available low-density lipoprotein particles (LDL)-based drug delivery system with the modification of T7 peptide ligand (T7-LDL). LDL, endogenous lipid transporters, can specifically bind to brain endothelial cells and glioma cells via interacting with the low-density lipoprotein receptors (LDLR). T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. By combining the dual-targeting delivery effect of T7 peptide and parent LDL, T7-LDL displayed higher glioma localization than that of parent LDL. After loading with VCR, T7-LDL showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that T7-LDL is an important potential drug delivery system for glioma-targeted therapy.

Long non-coding RNA LINC00174 promotes glycolysis and tumor progression by regulating miR-152-3p/SLC2A1 axis in glioma

“…In the twentieth century, with the development of molecular biology and oncogenetics, people have a better understanding of the genetic characteristics of glioma, which provides a new idea for the subsequent gene therapy of glioma. Therefore, at present, the international community is focusing on the search for effective gene markers of glioma, hoping to be conducive to early intervention treatment and early prognosis judgment of glioma [4–6].…”

The nanostructured secretome

“…LDLs loaded with chemotherapeutics were able to pass the BBB and accumulate into brain tissue showing a dose-dependent anti-tumor activity towards glioma cells. 111 Interestingly, gliomabearing mice repeatedly treated with intravenous injection of engineered LDLs showed significant tumor growth inhibition compared to saline, free drug, and native loaded LDLs promoting the highest animal survival rate. 111 The scientific literature describes a multitude of different approaches intended to manipulate and engineer both eukaryotic and prokaryotic EVs that range from passive or active drug loading, active targeting (see Section 4), click chemistry, and pH responsive EVs.…”

“…LDLs exposing on their surface the transferrin receptor ligand and loaded with chemotherapeutics were used as treatment for brain cancer. 111 Transferrin receptors are overexpressed in both blood brain barrier (BBB) and brain tumors cells. Therefore, engineered…”

Cellular and Molecular Mechanisms Underlying Glioblastoma and Zebrafish Models for the Discovery of New Treatments

“…Another approach consists of vincristine sulfate in powder form added to low-density lipoprotein (LDL, expressed in the endothelial cells of the BBB and glioma cells) NPs modified with the T7 peptide TfR ligand. This dual interaction is also effective in crossing the BBB and acting on GBM, but using LDL nanocarriers could be problematic in patients with high cholesterol levels [ 204 ]. Zou et al used monosialotetrahexosylganglioside (GM1) as a targeting ligand to improve the transport of DOX-loaded micelles through the BBB [ 205 ].…”