Introduction: Docetaxel (DTX) is a widely-used systemic treatment for metastatic prostate cancer (PC), but it has important, sometimes life-threatening, adverse effects. A novel drug delivery system obtained by covalent conjugation DTX and an anti-prostate specific membrane antigen (anti-PSMA) molecule (anti-FOLH1 monoclonal antibody) over mesoporous silica nanoparticles (MSN) has proved in-vitro to have a highly selective cell internalization and cytotoxic effect on PC cells overexpressing PSMA (LNCaP cell line). This innovative nanomedicine could be a targeted, precision therapy for intratumoral DTX delivery in PC, diminishing total DTX dose and the risk of side effects. In this study, we present our results after testing this nanomedicine by intratumoral delivery in a xenograft model using mice. Methods: Immunodeficient (NU/NU) nude mice were used. Mice were inoculated with LNCaP cells in the lap subcutaneous tissue. Every 4 days, tumor growth and mice weight were measured, and animal welfare was monitored. When calculated xenograft volume exceeded 150 mm3, treatments were inoculated every 4 days. Antitumoral effect was defined as a decrease in tumor volume. Humane endpoints for animal euthanizing were tumor growth >1000 mm3, severe distress, weight loss > 20% or extensive skin lesions. This study was approved by our Animal Testing Ethics Committee. Results: A total of 75 mice were included. Treatment groups were: intratumoral Phosphate-Buffered Saline solution (control group), intratumoral DTX (2 mg/Kg), intratumoral DTX (10 mg/Kg), intratumoral nanomedicine (MSN-DTX) , intratumoral targeted nanomedicine (MSN-DTX-antiPSMA), intravenous control (propielenglicol solution), intravenous DTX (2 mg/Kg) and intravenous nanomedicine (MSN-DTX). Antitumoral activity was significant for all treatments groups when compared to control groups. In groups treated with intratumoral nanomedicine (MSN-DTX) with and without conjugated anti-PSMA, the antitumoral activity was similar to groups treated with intratumoral DTX, but with a significantly lower total dose of DTX. At pathomorphological exam, necrosis was observed in tumor samples, but no signs of toxicity were observed. Conclusions: Docetaxel-conjugated mesoporous silica nanomedicines effectively reduced tumor volume in intratumoral administration using a nude mice PC xenograft model. These results are promising, paving the way for a future applicability as a precision intratumoral medicine for PC in humans. SOURCE OF Funding: None
