Exploring the potential of anti-PSMA peptide-conjugated mesoporous silica nanoparticles in Prostate Cancer therapy: an in vitro and in vivo evaluation

• Grant number: 24/22924-4
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: August 01, 2026
• End date: July 31, 2031
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Rafael Miguel Sábio
• Grantee: Rafael Miguel Sábio
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• City of the host institution: Araraquara
• Associated researchers: Christian Shleider Carnero Canales ; Fabio Montico ; Fernando Rogério Pavan ; Hélder Almeida Santos ; Sidney José Lima Ribeiro ; Valéria Helena Alves Cagnon Quitete
• Associated scholarship(s): 26/21339-6 - Tuftsin-Conjugated Mesoporous Silica Nanoparticles for Enhanced Cellular Internalization in Prostate Cancer Cells., BP.IC; 26/21599-8 - Exploring the potential of anti-PSMA peptide-conjugated mesoporous silica nanoparticles in prostate cancer therapy: an in vitro and in vivo evaluation, BP.JP

Abstract

Prostate cancer (PC) is one of the most common non-contagious diseases affecting men worldwide. Although treatment with the chemotherapy docetaxel (DTX) is clinically effective, it is associated with the development of resistance in more advanced stages of the disease. In addition, the DTX has low aqueous solubility and problems related to its pharmacokinetics. Mesoporous silica nanoparticles (MSNs) have attracted great interest due to their high chemical stability, large surface area, and tunable pores size and volume, which allow the incorporation of high amounts of drugs, protecting them from degradation and premature release processes, acting as excellent nanocarriers. Furthermore, the hydroxyls available on their surface allow the functionalization of alkoxysilane groups such as (3-glycidyloxypropyl) trimethoxysilane (GPTMS), which makes the nanosystems very reactive to specific molecules such as the anti-prostate-specific membrane antigen peptide (aPSMA), which binds to the PSMA receptor overexpressed in many prostate tumors, representing an innovative approach for the treatment of PC in combination with DTX. This Young Researcher (JP) Research grant proposal aims to consolidate my research group and implement an innovative research line at the Host Institution (FCF-UNESP-Araraquara) based on the design of smart DTX-loaded aPSMA-conjugated MSN-based nanosystems for PC treatment. This proposal aims to overcome drawbacks such as low internalization, lack of controlled drugs release on the target site, several side effects to the patient and low efficacy of the current treatments. To evaluate these parameters and prove their effectiveness, the characterization of the nanosystems will be performed, as well as in vitro assays using LNCaP and PC-3 cell lines models, and in vivo assays using a toxicity model in Galleria mellonella larvae and in transgenic adenocarcinoma for the mouse prostate (TRAMP) treated by intraperitoneal administration route. (AU)