The SR-B1 Receptor as a Potential Target for Treating Glioblastoma.

Ethan Berney,Nirupama Sabnis,Rob Dickerman,Andras G Lacko,Marlyn Panchoo,Sangram Raut

doi:10.1155/2019/1805841

Abstract

Purpose The goal of these studies was to provide proof of concept for a novel targeted therapy for Glioblastoma Multiforme (GBM). Methods. These studies involve the evaluation of reconstituted high density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for the drug, mammalian Target of Rapamycin (mTOR) inhibitor Everolimus (EVR) to GBM cells. Cytotoxicity studies and assessment of downstream effects, including apoptosis, migration, and cell cycle events, were probed, in relation to the expression of scavenger receptor B type 1 (SR-B1) by GBM cells. Results Findings from cytotoxicity studies indicate that the rHDL/EVR formulation was 185 times more potent than free EVR against high SR-B1 expressing cell line (LN 229). Cell cycle analysis revealed that rHDL/EVR treated LN229 cells had a 5.8 times higher apoptotic cell population than those treated with EVR. The sensitivity of GBM cells to EVR treatment was strongly correlated with SR-B1 expression. Conclusions These studies present strong proof of concept regarding the efficacy of delivering EVR and likely other agents, via a biocompatible transport system, targeted to the SR-B1 receptor that is upregulated in most cancers, including GBM. Targeting the SR-B1 receptor could thus lead to effective personalized therapy of GBM.

Highlights

Glioblastoma Multiforme (GBM) is a devastating disease with a very poor prognosis, as the survival of patients with GBM rarely extends beyond 3 years from the time of diagnosis [1,2,3]
The EVR loading efficiency into the reconstituted high density lipoprotein (rHDL) Nanoparticle scavenger receptor type B1 (SR-B1) (NP) was similar to formulations described earlier [22]
The particle diameter analyses obtained from dynamic light scattering (DLS) measurements for the rHDL/ EVR NPs (Figure 1) show a mean diameter of 20.6 nm ± 5.8 nm

Summary

Introduction

Glioblastoma Multiforme (GBM) is a devastating disease with a very poor prognosis, as the survival of patients with GBM rarely extends beyond 3 years from the time of diagnosis [1,2,3]. Despite intensive research and new approaches to treatment, only limited improvements in patient outcomes have been achieved [4, 5]. Perhaps involving nanotechnology, are urgently needed to improve the survival and the quality of life for GBM patients. Postoperative hypoxia is likely to facilitate diffuse and invasive tumor growth [7] in addition to enhancing the expression of the scavenger receptor type B1 (SR-B1) [8]. Targeting GBM with a high density lipoprotein (HDL) type drug transporter may be effective against the invasion of GBM tumors, facilitated by the SR-B1 receptor [9]

Objectives

Methods

Results

Conclusion