Design and Testing of Dual-Targeted Gd3N@C80-Containing Glioblastoma Theranostics

Getachew Tedla,Anthony Dellinger,Jesse Plotkin,Christopher Kepley

doi:10.1155/2019/1242930

Getachew Tedla, Anthony Dellinger + Show 2 more

Open Access

https://doi.org/10.1155/2019/1242930

Copy DOI

Abstract

The majority of the malignant brain tumors are gliomas with glioblastoma being the most common and aggressive type. Due to its extreme infiltrative nature and higher occurrence frequency, finding new glioblastoma therapeutics and diagnostics is a high priority. In line with this, we previously synthesized a glioblastoma-targeting theranostic that images and delivers a therapeutic payload of doxorubicin (DXR) to human xenograft tumors. Herein, a dual-targeted theranostic is synthesized on the hypothesis that targeting multiple receptors would enhance delivery precision. Doxorubicin and endo-fullerene (Gd3N@C80) were encapsulated within liposomes and conjugated with transferrin (Tf) and lactoferrin (Lf). The hydrodynamic size, zeta potential, encapsulation efficiency, and tagging with proteins of the Gd3N@C80- and DXR-loaded liposomes were characterized using dynamic light scattering (DLS), inductively coupled plasma (ICP) mass spectrometer, Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible (UV-Vis) spectrophotometry analysis. As verification of efficacy, the Tf and Lf dual-tagged theranostic liposomes were able to significantly induce cell death compared to Lf monotagged theranostics.

Highlights

Close to 80,000 new glioma cell-involved primary central nervous system (CNS) tumors are diagnosed each year in the United States with roughly half being malignant [1, 2]
The UV-Vis and Fourier-transform infrared spectroscopy (FTIR) spectra measurements support the successful conjugation of proteins to the liposomes as depicted by a clear difference in the absorbance signatures of those protein-tagged liposomes compared to nontagged counterparts
Novel theranostic liposomes tagged with both Lf and Tf (1 : 1 ratio) are constructed for the first time to harness the potential of crossing the blood-brain barrier (BBB) and kill transferrin receptor expressing glioblastoma multiforme (GBM) and glioma stem cells

Summary

Introduction

Close to 80,000 new glioma cell-involved primary central nervous system (CNS) tumors are diagnosed each year in the United States with roughly half being malignant [1, 2]. Glioblastoma multiforme (GBM), a World Health Organization grade IV glioma, is the most common and lethal primary malignancy of the central nervous system [5]. Targeted delivery of therapeutics in GBMs mainly relies on single biomarkers, and the chemotherapeutics suffer from the lack of specificity causing significant healthy cells’ death. Another major obstacle for any GBM diagnostic or therapy is transporting it across the blood-brain barrier (BBB)

Objectives

Methods

Results

Conclusion