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

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dc.contributor.authorAlhussan, Abdulaziz
dc.contributor.authorJackson, Nolan
dc.contributor.authorEaton, Sarah
dc.contributor.authorDos Santos, Nancy
dc.contributor.authorBarta, Ingrid
dc.contributor.authorZaifman, Josh
dc.contributor.authorChen, Sam
dc.contributor.authorTam, Yuen Y.C.
dc.contributor.authorKrishnan, Sunil
dc.contributor.authorChithrani, Devika B.
dc.date.accessioned2023-10-15T13:53:46Z
dc.date.available2023-10-15T13:53:46Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.description.abstractCurrent 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis study was funded by the Kuwait Foundation for the Advancement of Sciences (KFAS) under project code CB21-63SP-01; the Nanomedicines Innovation Network Strategic Initiative fund (NMIN-SI); the John R. Evans Leaders Fund (JELF) from the Canada Foundation for Innovation (CFI) and the British Columbia Knowledge Development Fund (BCKDF); an NSERC Discovery grant from the Natural Sciences and Engineering Research Council of Canada (NSERC); grants R01CA257241, R01DE028105, R21CA252156, and R01CA274415 from the National Institutes of Health (NIH) of United States of America; and a collaborative health grant from the University of Victoria.en_US
dc.identifier.citationAlhussan, A., Jackson, N., Eaton, S., Santos, N. D., Barta, I., Zaifman, J., Chen, S., Tam, Y. K., Krishnan, S., & 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/cancers14246137en_US
dc.identifier.urihttps://doi.org/10.3390/cancers14246137
dc.identifier.urihttp://hdl.handle.net/1828/15528
dc.language.isoenen_US
dc.publisherCancersen_US
dc.subjectgold nanoparticlesen_US
dc.subjectdocetaxelen_US
dc.subjectlipid nanoparticlesen_US
dc.subjectpancreatic canceren_US
dc.subjectnanomedicineen_US
dc.titleLipid-Nanoparticle-Mediated Delivery of Docetaxel Prodrug for Exploiting Full Potential of Gold Nanoparticles in the Treatment of Pancreatic Canceren_US
dc.typeArticleen_US

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