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

Bone-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...

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Published in:Pharmaceutics 2023-02, Vol.15 (2), p.662
Main Authors: Lampe, Jana B, Desai, Priyanka P, Tripathi, Amit K, Sabnis, Nirupama A, Chen, Zhe, Ranjan, Amalendu P, Vishwanatha, Jamboor K
Format: Article
Language:English
Subjects:
alendronate
Androgens
bone-targeting
cabazitaxel
Cancer therapies
Care and treatment
Cell growth
Chemical properties
Development and progression
Drugs
epithelial-to-mesenchymal transition (EMT)
FDA approval
Health aspects
Hypercalcemia
L-lactide-co-glycolide) nanoparticles
Metastasis
Nanoparticles
poly(D
Polyvinyl alcohol
Prostate cancer
Tumors
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Summary:Bone-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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15020662