Evaluation of cetuximab-modified porous silicon nanoparticles as docetaxel carrier to prostate cancer treatment

• Grant number: 22/02661-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2023
• End date: February 26, 2024
• Field of knowledge: Engineering - Materials and Metallurgical Engineering
• Principal Investigator: Marlus Chorilli
• Grantee: Rafael Miguel Sábio
• Supervisor: Helder Almeida Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University Medical Center Groningen (UMCG), Netherlands
• Associated to the scholarship: 18/25377-3 - Potential evaluation of cetuximab-modified mesoporous silica nanoparticles as docetaxel carrier to prostate cancer treatment., BP.PD

Abstract

Prostate cancer (PCa) is one of the most non-contagious diseases that affects the male population in the world. Although clinically effective, the chemotherapy treatment with docetaxel (DTX) is associated with the development of resistance in more advanced stages of the disease. Besides, DTX presents low aqueous solubility and drawbacks related to its pharmacokinetics. Porous silicon nanoparticles (PSi) have attracted great interest due to their biocompatibility, high chemical stability, large surface area and tunable pore diameters and volumes, allowing the incorporation of large amounts of drugs, protecting them from deactivation and degradation processes besides avoids premature release acting as an excellent nanocarrier. In addition, the hydroxyls groups available on its surface allow the conjugation of molecules such as the monoclonal antibody cetuximab (CTX) which binds to the overexpressed Enhanced Growth Factor Receptor (EGFR) in many prostate tumors, representing a potential strategy for the treatment of prostate cancer associated to DTX. Taking into account all aforementioned, the goal of this proposal is to design smart PSi-based nanoplatforms containing DTX inside the pores functionalized with CTX to PCa treatment. This proposal aims to overcome drawbacks as low internalization, premature release before to reach the target site, several side effects to the patient and low effectiveness of the current treatments. In order to evaluate these parameters, materials characterization and methods validation will be carried out as well as in vitro assays using PC-3 and DU145 cells line models and in vivo assays from animal model aiming to prove the efficacy of the new smart nanocarriers. (AU)