Lipid-nanoparticle-mediated delivery of docetaxel prodrug for exploiting full potential of gold nanoparticles in the treatment of pancreatic cancer

Date

2022

Authors

Alhussan, Abdulaziz
Jackson, Nolan
Eaton, Sarah
Dos Santos, Nancy
Barta, Ingrid
Zaifman, Josh
Chen, Sam
Tam, Yuen Yi C.
Krishnan, Sunil
Chithrani, Devika B.

Journal Title

Journal ISSN

Volume Title

Publisher

Cancers

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 (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.

Description

Keywords

gold nanoparticles, docetaxel, lipid nanoparticles, pancreatic cancer, nanomedicine

Citation

Alhussan, A., Jackson, N., Eaton, S., Dos Santos, N., Barta, I., Zaifman, J., . . . Chithrani, D. B. (2022). “Lipid-nanoparticle-mediated delivery of docetaxel prodrug for exploiting full potential of gold nanoparticles in the treatment of pancreatic cancer.” Cancers, 14(24), 6137. https://doi.org/10.3390/cancers14246137