Development of novel solid lipid nanoparticles for delivery of astrakurkurone with increasing anti-cancer efficacy against non-small cell lung cancer cells.

Lipid nanoparticles (LNPs) are a highly effective tool for combating cancer by delivering anti-cancer drug molecules specifically to tumor sites while avoiding healthy cells. Alcohol dehydrogenase (ADH) is over-expressed in cancer cells compared to non-cancerous cells. To leverage this difference, we developed a novel formulation, astrakurkurone encapsulated in PEGylated lipid nanoparticles (Astra SLNP), derived from fatty alcohol that serve as substrates for ADH leading to preferential uptake and metabolism by cancer cells, which then release astrakurkurone into the cellular matrix. Astrakurkurone, a sesquiterpenoid derived from Astraeus hygrometricus, a wild edible mushroom, has been established in numerous studies to possess potent anti-cancer properties by inducing apoptosis and inhibiting cancer cell proliferation. Our study indicated that the novel Astra-SLNP (98.89 ± 20.86 nm in size, with a negatively charged surface [zeta-potential: -10 mV]) exhibited significantly 10-fold higher anti-cancer efficacy compared to free astrakurkurone against lung cancer A549 cells. Moreover, MTT assays confirmed that Astra-SLNP showed no significant cytotoxicity towards non-cancerous cells (human embryonic kidney, HEK293 cells).The morphological changes in apoptotic cells were investigated using phase-contrast, bright-field, scanning electron microscopy (SEM), field emission scanning electron microscopy (FESEM) and fluorescence microscopy with AnnexinV-FITC/PI staining protocol. Cellular uptake and degradation of lipid nanoparticles studies demonstrated dose-dependent uptake and time-dependent cellular degradation. In addition, scratch assay, colony formation assay, and the evaluation of mitochondrial membrane potential further suggested that Astra-SLNP possessed better anti-cancer potency than free astrakurkurone.