Photophysical Characterization and In Vitro Evaluation of a-Mangostin-Loaded HDL Mimetic Nano-Complex in LN-229 Glioblastoma Spheroid ModelShow full item record

Title	Photophysical Characterization and In Vitro Evaluation of a-Mangostin-Loaded HDL Mimetic Nano-Complex in LN-229 Glioblastoma Spheroid Model
Author	Kapic, Ammar; Sabnis, Nirupama; Dossou, Akpedje S.; Chavez, Jose; Ceresa, Luca; Gryczynski, Zygmunt; Fudala, Rafal; Dickerman, Rob; Bunnell, Bruce A.; Lacko, Andras G.
Date	7/5/2024
Description	Cytotoxic activity has been reported for the xanthone alpha-mangostin (AMN) against Glioblastoma multiforme (GBM), an aggressive malignant brain cancer with a poor prognosis. Recognizing that AMN's high degree of hydrophobicity is likely to limit its systemic administration, we formulated AMN using reconstituted high-density lipoprotein (rHDL) nanoparticles. The photophysical characteristics of the formulation, including fluorescence lifetime and steady-state anisotropy, indicated that AMN was successfully incorporated into the rHDL nanoparticles. To our knowledge, this is the first report on the fluorescent characteristics of AMN with an HDL-based drug carrier. Cytotoxicity studies in a 2D culture and 3D spheroid model of LN-229 GBM cells and normal human astrocytes showed an enhanced therapeutic index with the rHDL-AMN formulation compared to the unincorporated AMN and Temozolomide, a standard GBM chemotherapy agent. Furthermore, treatment with the rHDL-AMN facilitated a dose-dependent upregulation of autophagy and reactive oxygen species generation to a greater extent in LN-229 cells compared to astrocytes, indicating the reduced off-target toxicity of this novel formulation. These studies indicate the potential therapeutic benefits to GBM patients via selective targeting using the rHDL-AMN formulation.
Link	https://doi.org/10.3390/ijms25137378 https://repository.tcu.edu/handle/116099117/65965
Department	Physics and Astronomy