Lipid-Nanoparticle-Mediated Delivery of Docetaxel Prodrug for Exploiting Full Potential of Gold Nanoparticles in the Treatment of Pancreatic Cancer

SIMPLE SUMMARY: Pancreatic cancer is one of the leading causes of cancer deaths worldwide. The use of nanoparticles as radiosensitizers and drug delivery vehicles could open the door to solving many of the obstacles in current cancer treatments. Gold nanoparticles (GNPs) and docetaxel (DTX) have shown very promising synergetic radiosensitization effects, despite DTX toxicity to normal tissues. In this paper, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNP(DTX-P)) on GNP uptake in pancreatic cancer models in vitro and in vivo. The results show that LNP(DTX-P)-treated tumour samples have twice the amount of GNP uptake in both in vitro and in vivo models. These very promising results establish that LNP(DTX-P) have very similar outcomes to free DTX on tumour tissues. These results demonstrate the potential of incorporating GNPs and LNP(DTX-P) as radiosensitization tools to current radiotherapy protocols for improved tumour targeting. ABSTRACT: Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNP(DTX-P)) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNP(DTX-P). For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously in NRG mice, and the mice were dosed with 2 mg/kg of GNPs and 6 mg/kg of DTX or an equivalent dose of LNP(DTX-P). The results show that LNP(DTX-P)-treated tumour samples had double the amount GNPs compared to control samples, both in vitro and in vivo. The results are very promising, as LNP(DTX-P) have superior targeting of tumour tissues compared to free DTX due to their nanosize and their ability to be functionalized. Because of their minimal toxicity to normal tissues, both GNPs and LNP(DTX-P) could be ideal radiosensitization candidates in radiotherapy and would produce very promising synergistic therapeutic outcomes.