A calcium phosphate drug carrier loading with 5-fluorouracil achieving a synergistic effect for pancreatic cancer therapy

Calcium based biomaterials were widely used for drug delivery application due to their biodegradability, biocompatibility, and high drug loading capacity. Herein, amino-capped polyamidoamine (PAMAM) dendrimer was applied as a macromolecular template to form amino-modified calcium phosphate hollow sphere (CaPO-NH₂). After loading with 5-fluorouracil (5Fu), this system performed synergistic Cancer chemotherapy. In this study, the 5Fu/CaPO-NH₂ particles could be efficiently uptaken by Cancer cells, and then decompose into CA²⁺ and release 5Fu drug in the cytoplasm; therefore calcium overload and Reactive Oxygen Species (ROS) accumulation were found in PSN1 cells that could induce cell membrane damage and elicit cell Apoptosis through a series of biochemical reactions including endoplasmic reticulum stress, lipid peroxidation and mitochondrial Apoptosis. In the PSN1 pancreatic Cancer xenograft model, the 5Fu/CaPO-NH₂ system performed high tumor inhibition via chemotherapy and calcium overload induced Apoptosis. Comparingly, the normal cells and organs were insensitive to this synergistic therapy, which indicated the well biocompatibility of delivery system. Thus, this study provided a promising CaPO-NH₂ drug delivery platform for enhanced 5Fu chemotherapeutic effect.

Calcium overload; Calcium phosphate; Endoplasmic reticulum stress; Pancreatic cancer; Reactive oxygen species.