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 (LNPDTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. The results show that LNPDTX-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 LNPDTX-P have very similar outcomes to free DTX on tumour tissues. These results demonstrate the potential of incorporating GNPs and LNPDTX-P as radiosensitization tools to current radiotherapy protocols for improved tumour targeting. 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 (LNPDTX-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 LNPDTX-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 LNPDTX-P. The results show that LNPDTX-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 LNPDTX-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 LNPDTX-P could be ideal radiosensitization candidates in radiotherapy and would produce very promising synergistic therapeutic outcomes.

Automated summary

Pancreatic cancer is a major cause of cancer deaths worldwide. The use of nanoparticles as radiosensitizers and drug delivery vehicles can overcome current obstacles in cancer treatments. The study found that a DTX prodrug encapsulated in lipid nanoparticles can enhance the uptake of gold nanoparticles in pancreatic cancer, providing a potential strategy for radiotherapy.