Photophysical Characterization and In Vitro Evaluation of α-Mangostin-Loaded HDL Mimetic Nano-Complex in LN-229 Glioblastoma Spheroid Model

• Published in: International journal of molecular sciences 2024-07, Vol.25 (13), p.7378
• Main Authors: Kapic, Ammar, Sabnis, Nirupama, Dossou, Akpedje S, Chavez, Jose, Ceresa, Luca, Gryczynski, Zygmunt, Fudala, Rafal, Dickerman, Rob, Bunnell, Bruce A, Lacko, Andras G
• Format: Article
• Language: English
• Subjects: Anisotropy; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Astrocytes - drug effects; Astrocytes - metabolism; Autophagy - drug effects; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cancer therapies; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Cholesterol; Cyclin-dependent kinases; Cytotoxicity; Drug Carriers - chemistry; Drug delivery systems; Drug dosages; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Glioma; Humans; Kinases; Leukemia; Lipoproteins; Lipoproteins, HDL - chemistry; Lipoproteins, HDL - metabolism; Medical prognosis; Nanoparticles; Nanoparticles - chemistry; Reactive oxygen species; Reactive Oxygen Species - metabolism; Spheroids, Cellular - drug effects; Toxicity; Tumors; Xanthones - chemistry; Xanthones - pharmacology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25137378

Cytotoxic activity has been reported for the xanthone α-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.