NanoCEA-CESPU-2018: Development of antibody-functionalized PLGA-PEG nanoparticles to target the carcinoembryonic antigen receptor on colorectal cancer
admin-cespu
Principal Investigator:
Bruno Sarmento (bruno.sarmento@iucs.cespu.pt)
Leader Institution:
CESPU
Research Team:
Bruno Sarmento, Rui Moura, Maria José Oliveira, Inês Pereira, Flávia Sousa, Andreia Almeida, Ana Rita Sousa, Francisca Araújo
Funding entity:
CESPU
Budget:
5000€
Period covered:
2018-2019
Abstract:
Colorectal cancer (CRC) represents one of the most common cancer-related cause of death with a high 5-year prevalence posttreatment worldwide. Standard chemotherapies currently available, such as paclitaxel (PTX), exhibit a poor water solubility, high toxicity and even gene therapies (as siRNA) have a poor stability in biological fluids, rendering low efficacy. Carcinoembryonic antigen (CEA) is a biomarker used for preoperative evaluation and postoperative follow-up of CRC patients. This project proposes to develop PTX and siRNA-loaded nanoparticles to target the CEA receptor on CRC. Polymeric nanoparticles of poly(lactic-coglycolic acid) (PLGA) and poly(ethylene glycol) (PEG), will be loaded with PTX or siRNA against MACC1 and further surfacefunctionalized with a monoclonal CEA antibody and a CEA single chain variable fragment (scFv), in a site-oriented manner. Nanoparticles will be tested for physical-chemical properties, cytotoxicity, cell cycle effect and apoptosis/necrosis quantification on colorectal cancer cell lines, and drug penetration in intestinal cell monolayers. It is foreseen that nanoparticles targeting CEA will be useful as a therapeutic strategy for CRC.
Colorectal cancer (CRC) represents one of the most common cancer-related cause of death with a high 5-year prevalence posttreatment worldwide. Standard chemotherapies currently available, such as paclitaxel (PTX), exhibit a poor water solubility, high toxicity and even gene therapies (as siRNA) have a poor stability in biological fluids, rendering low efficacy. Carcinoembryonic antigen (CEA) is a biomarker used for preoperative evaluation and postoperative follow-up of CRC patients. This project proposes to develop PTX and siRNA-loaded nanoparticles to target the CEA receptor on CRC. Polymeric nanoparticles of poly(lactic-coglycolic acid) (PLGA) and poly(ethylene glycol) (PEG), will be loaded with PTX or siRNA against MACC1 and further surfacefunctionalized with a monoclonal CEA antibody and a CEA single chain variable fragment (scFv), in a site-oriented manner. Nanoparticles will be tested for physical-chemical properties, cytotoxicity, cell cycle effect and apoptosis/necrosis quantification on colorectal cancer cell lines, and drug penetration in intestinal cell monolayers. It is foreseen that nanoparticles targeting CEA will be useful as a therapeutic strategy for CRC.
Project area: