• The in vitro studies performed show these nanomedicines improve docetaxel antitumor activity, the most current drug in prostate cancer treatment, by one hundred fold. The study has been developed by researchers at the Universitat Politècnica de València (UPV), the Spanish National Research Council (CSIC), the Hospital Universitari i Politècnic La Fe and the Principe Felipe Research Center (CIPF).
• Researchers have also been developed a nanomarker, which determines accurately tumor tissue location, facilitating disease diagnosis at the initial stage

In Europe, prostate cancer is the most common form of cancer in men, with a greater incidence of 100 cases per 100,000 men. In addition, it is the second most common cause of cancer death in men today.

This pathology mainly affects elder men: nine out of 10 deaths occur after 65 years. Therefore, it represents a very important concern for health in developed countries, where the population of elder men is the majority. In this context, although docetaxel is the most used chemotherapy for hormone-resistant prostate cancer, its high systemic toxicity limits both the dose and duration of therapy, which significantly reduces its antitumor efficacy.

Now, a research team of the Universitat Politècnica de València (UPV), the Spanish National Research Council (CSIC), the Hospital Uni­versitari i Politècnic La Fe and the Principe Felipe Research Center (CIPF), has developed a new nanomedicine to treat non-metastasic prostate cancer.

The tests carried out open the door to the future application of very effective treatments at very low doses of docetaxel. This novel nanomedicine would be administered by intraprostatic injection, without minimum secondary effect over healthy tissue. Completed in vitro studies have shown this system improves docetaxel antitumor activity (current drug for prostate cancer treatment) by one hundred fold.

“In vitro studies with this nanomedicine on prostate cancer cells over-expressing PSMA (prostate-specific membrane antigen) receptors showed docetaxel antitumor activity improvement up to one hundred fold”, emphasizes Pablo Botella, researcher at the Instituto de Tecnología Química (ITQ), joined center of UPV and CSIC.

After completing the in vitro study, the work is currently doing in vivo preclinical testing. Meanwhile, it is expected to start a phase I clinical trial over a small patient group in no longer than two years.

Facilitating diagnosis

Furthermore, researchers have also developed a new nanomarker which enables tumor tissue labeling in prostate with high accuracy. “Thanks to PET image technique, radioactive isotope labeled nanomedicine is able to locate the malign tissue in the gland with unicellular precision, which will facilitate early disease diagnosis”, adds Botella.

These results have been published in the journal ACS Omega of the American Chemical Society.

How is the new nanomedicine?

The new nanomedicine developed is a system based on mesoporous silica nanoparticles functionalized with docetaxel and a monoclonal antibody (anti-FOLH1) that selectively interacts with PSMA receptors of prostate cancer cells. The system presents great stability in biological fluids and all components have been approved by the Food and Drug Administration (FDA, United States of America) for clinical use.

The presence of the monoclonal antibody promotes nanomedicine cell internalization into malignant cells (at least 25% higher than the free drug, as the naked molecule shows no tumor selectivity). Furthermore, the use of a specific docetaxel linking protocol to nanoparticles provides selective drug release inside cancer cells.

CURSOL foundation and TERACAP project

This work was initially funded by CURSOL (Valencian Community Resort and Solidarity Culture) foundation, and is currently fitted in TERACAP project, which is supported by Valencian Community government, and whose principal investigator is Prof. Jose María Benlloch, Director of Molecular Imaging Instrumentation Institute (I3M), joined center of UPV and CSIC.

In this project, together with I3M, ITQ Nanomedicine’s Team (headed by Dr. Pablo Botella) is also involved. Furthermore, a team of Hospital Uni­versitari i Politècnic La Fe (headed by Dr. Cesar David Vera-Donoso), and another from CIPF (headed by Dr. Victoria Moreno), supervise in vivo preclinical testing and clinical trials.

Reference

E. Rivero-Buceta, C, Vidaurre-Agut, C.D. Vera Donoso, J.M. Benlloch, V. Moreno-Manzano, P. Botella, “PSMA-Targeted mesoporous silica nanoparticles for selective intracellular delivery of docetaxel in prostate cancer cells”, ACS Omega, vol. 4, n. 1, p. 1281, 2019