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RGD Tripeptide Functionalized Polymeric Nanoparticles for Targeted Delivery of 5-Fluorouracil in the Treatment of Colorectal Cancer

Grant number: 23/09154-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2023
Effective date (End): July 31, 2024
Field of knowledge:Physical Sciences and Mathematics - Physics - Condensed Matter Physics
Principal Investigator:Valtencir Zucolotto
Grantee:Ana Laura Moreno Martins Sanchez
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Cancer is among the leading causes of mortality worldwide, with colorectal cancer being the second most lethal, presenting a high incidence globally, surpassed only by lung cancer. In Brazil, it is estimated that the number of cases will increase in the next three years, with women being the most affected. 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapy drugs for colorectal tumor treatment. However, like other drugs, 5-FU has certain limitations, especially regarding the side effects caused by damage to non-tumor cells. Therefore, it becomes necessary to explore alternatives that can optimize chemotherapy and patient well-being. One innovative tool to improve the anticancer activity of chemotherapeutic agents is the use of a controlled release system. These systems can reduce side effects, increase efficacy, solubility in aqueous environments, selectivity, and safety of these drugs. One example of such systems is poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles. They are polymeric nanocarriers widely employed in nanomedicine due to their low toxicity, as the released lactic and glycolic acids are easily metabolized by the body. ±v²3 integrins are cell surface receptors overexpressed in tumor cells and have a high affinity for the RGD (arginine-glycine-aspartate) tripeptide sequence. Thus, functionalizing nanoparticles modified by RGD for active targeting is a promising strategy. Therefore, this project aims to develop a system composed of RGD-functionalized polymeric nanoparticles to encapsulate 5-FU in order to achieve a more targeted and effective chemotherapy treatment. It is expected that incorporating this agent into a delivery system will enhance its stability and optimize its action in cancer cells, contributing to research and studies on colorectal cancer treatments.

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