Cabazitaxel-Loaded Nanoparticles Reduce the Invasiveness in Metastatic Prostate Cancer Cells: Beyond the Classical Taxane Function

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dc.creatorLampe, Jana B.
dc.creatorDesai, Priyanka P.
dc.creatorTripathi, Amit K.
dc.creatorSabnis, Nirupama A.
dc.creatorChen, Zhe
dc.creatorRanjan, Amalendu P.
dc.creatorVishwanatha, Jamboor K.
dc.creator.orcid0000-0002-0266-6020 (Vishwanatha, Jamboor K.)
dc.creator.orcid0000-0002-3641-7751 (Ranjan, Amalendu P.)
dc.date.accessioned2023-03-27T15:24:25Z
dc.date.available2023-03-27T15:24:25Z
dc.date.issued2023-02-26
dc.description.abstractBone-metastatic prostate cancer symbolizes the beginning of the later stages of the disease. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. We hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuated the EMT marker, Vimentin, and led to an increased E-cadherin expression. These changes impart epithelial characteristics and inhibit invasive properties in cancer progression. Consequently, progression to distant sites is also mitigated. We observed the reduction of phosphorylated Src at tyrosine 416, along with increased expression of phosphorylated cofilin at serine 3. These changes could affect migration and invasion pathways in cancer cells. Both increased p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for metastatic prostate cancer by inhibiting EMT, invasion, and migration, in prostate cancer cells.
dc.description.sponsorshipThis research was supported by National Institute of Health, grant number S21MD012472 to Jamboor K. Vishwanatha. The cryo-EM study was performed in collaboration with the Structural Biology Laboratory and the Cryo-Electron Microscope Facility at UT Southwestern Medical Center, which are partially supported by grant RP170644 from the Cancer Prevention & Research Institute of Texas (CPRIT) for cryo-EM studies.
dc.identifier.citationLampe, J. B., Desai, P. P., Tripathi, A. K., Sabnis, N. A., Chen, Z., Ranjan, A. P., & Vishwanatha, J. K. (2023). Cabazitaxel-Loaded Nanoparticles Reduce the Invasiveness in Metastatic Prostate Cancer Cells: Beyond the Classical Taxane Function. Pharmaceutics, 15(2), 662. https://doi.org/10.3390/pharmaceutics15020662
dc.identifier.issn1999-4923
dc.identifier.issue2
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32067
dc.identifier.volume15
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/pharmaceutics15020662
dc.rights.holder© 2023 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePharmaceutics
dc.subjectalendronate
dc.subjectbone-targeting
dc.subjectcabazitaxel
dc.subjectepithelial-to-mesenchymal transition (EMT)
dc.subjectpoly(D; L-lactide-co-glycolide) nanoparticles
dc.subjectprostate cancer
dc.titleCabazitaxel-Loaded Nanoparticles Reduce the Invasiveness in Metastatic Prostate Cancer Cells: Beyond the Classical Taxane Function
dc.typeArticle
dc.type.materialtext

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