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

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.

Green nanomedicine: the path to the next generation of nanomaterials for diagnosing brain tumors and therapeutics?

“…More recently, DOX and an imaging agent (Gd3N@C80, MRI contrast) were encapsulated within the liposomes and conjugated with transferrin (the ligand for the receptor that is expressed on glioma cells and glioma stem cells) and lactoferrin (targeting ligand for GBM). These dual-tagged theranostic nanosystems exhibited improved inhibitory effects in U251-MG cells compared to Lf monotagged counterparts [69].…”