Rapid and green radiation-induced synthesis of smart gold nanohybrids functionalized with cationic pullulan for effective anticancer drug delivery systems.

Herein, this study presents for the first time a rapid and green radiation-induced synthesis of smart gold nanohybrids stabilized/capped/functionalized with cationic pullulan (GNHs@C-PUL) for 5Fu delivery, aiming to improve intracellular uptake, efficacy, and safety of anticancer drugs. The systematically optimized synthesis condition for controlling the morphology and particle size of multifunctional GNHs@C-PUL were identified as pH = 8 with 1.5 %(w/v) C-PUL and a gamma radiation dose of 2 kGy. The pH-responsive GNHs@C-PUL were fully characterized and exhibited a spherical shape with a homogeneous particle size of approximately 6.88 ± 1.95 nm. 5Fu was successfully loaded onto spherical GNHs@C-PUL to form newly formulated 5Fu-GNHs@C-PUL (10.10 ± 2.94 nm) via intermolecular interactions, exhibiting a faster release rate under acidic conditions (pH 5.3) with 72.86 % released over 48 h. Interestingly, the self-assembled 5Fu-GNHs@C-PUL (IC50 = 47.85 μM) exhibited efficient intracellular uptake via endocytosis and enhanced the anticancer activity of 5Fu against MCF7 cells by up to 4.94-time compared to free 5Fu (IC50 = 236.20 μM). Moreover, this system also induced cell cycle arrest at the G0-G1 phase by 11.33 % and substantially increased the proportion of total apoptotic cells by 30.15 % compared to free 5Fu. These results suggest that the newly developed 5Fu-GNHs@C-PUL can be considered a promising candidate nanocarrier for effective anticancer drug delivery systems.