Photophysical Characterization and In Vitro Evaluation of α-Mangostin-Loaded HDL Mimetic Nano-Complex in LN-229 Glioblastoma Spheroid Model.
Ammar KapicNirupama SabnisAkpedje S DossouJose ChavezLuca CeresaZygmunt GryczynskiRafal FudalaRob DickermanBruce A BunnellAndras G LackoPublished in: International journal of molecular sciences (2024)
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.
Keyphrases
- poor prognosis
- high density
- drug delivery
- induced apoptosis
- long non coding rna
- cell cycle arrest
- end stage renal disease
- newly diagnosed
- reactive oxygen species
- oxidative stress
- signaling pathway
- healthcare
- cell death
- chronic kidney disease
- endoplasmic reticulum stress
- prognostic factors
- emergency department
- cell proliferation
- squamous cell carcinoma
- quantum dots
- white matter
- single molecule
- combination therapy
- subarachnoid hemorrhage
- patient reported outcomes
- case control
- locally advanced
- smoking cessation