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PSMA-Targeted Mesoporous Silica Nanoparticles for Selective Intracellular Delivery of Docetaxel in Prostate Cancer Cells

AuthorsRivero-Buceta, Eva CSIC; Vidaurre-Agut, Carla; Vera-Donoso, Cesar David; Benlloch Baviera, José María; Moreno-Manzano, Victoria; Botella Asunción, Pablo CSIC ORCID
Issue Date15-Jun-2019
PublisherACS Publications
CitationACS Omega 4(1): 1281-1291 (2019)
AbstractAlthough docetaxel is currently broadly used in prostate cancer treatment, poor water solubility and systemic toxicity limit the dose and duration of therapy. In this context, although different nanoplatforms have been proposed to overcome these issues, selective therapy needs developing methodologies to target malignant cells and minimizing the impact on healthy tissue. We here present a novel drug delivery system obtained by covalent conjugation of docetaxel and an anti-prostate specific membrane antigen (PSMA) molecule (anti-FOLH1 monoclonal antibody, clone C803N) over mesoporous silica nanoparticles. This conjugate remains stable in physiological medium and shows high selectivity for LNCaP, a specific cell line that overexpresses PSMA. As a consequence, cell internalization is increased by 25%. Furthermore, cytotoxic activity of the targeted system increases by 2-fold with regard to nontargeted nanoparticles and by 2 orders with regard to the naked drug. Conversely, no targeting effect is observed over PC3, a nonbearing PSMA cell line. We expect that this therapeutic system shows strong potential for treating nonmetastatic prostate cancer, mostly through intraprostatic administration.
Publisher version (URL)
Identifiersdoi: 10.1021/acsomega.8b02909
issn: 2470-1343
Appears in Collections:(ITQ) Artículos

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