Biomimetic nanoparticles coated with cell membranes as an innovative strategy in lung cancer therapy

• Grant number: 22/01434-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2022
• Effective date (End): February 28, 2026
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Valtencir Zucolotto
• Grantee: Maria Julia Bistaffa
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy, AP.TEM

Abstract

Lung cancer has the second highest incidence worldwide, with an estimated 2.2 million new cases and 1.8 million deaths during the year 2020. Platinum derivatives, such as cisplatin, are chemotherapeutic agents used for more than 40 years in the treatment of lung cancer, and its clinical application faces problems related to chronic dose-dependent adverse effects. The non-selective distribution and acquired resistance of tumor cells make it necessary to administer high doses, contributing to the toxicity of adjacent normal and healthy cells. Nanotechnology represents a great advance for the therapeutic and diagnostic areas focused on neoplasms. Polymer-based nanoparticles, such as poly (lactic acid-co-glycolic acid; PLGA), are promising alternatives for cancer treatment, due to their non-toxicity, biocompatibility, biodegradability and low cost. In order to escape the immune system and reach tumor tissue, nanoparticles can be coated with cell membranes. This strategy offers specificity to the cells of interest, contributing to lower toxicity in adjacent healthy cells. In this PhD project, we propose the development of PLGA nanoparticles containing cisplatin coated with hybrid membranes of T lymphocytes and lung tumor cells (A549) as an innovative strategy in the therapy against lung cancer. A549 cells express a high rate of surface adhesion proteins that contribute to the specific targeting of nanostructures to the tumor site. Additionally, T lymphocyte membranes are favorable to evasion of biological barriers of the phagocytic immune system. As far as we know, there is no record in the literature of the use of hybrid cell membranes of T lymphocytes and A549 cells. In this sense, the proposed innovation may represent a strategy of great interest and potential for oncological application. The nanoparticles will be synthesized and their physical-chemical properties will be systematically characterized. The in vitro and in vivo performance (internalization, cytotoxicity and antitumor activity) of the nanoparticles will be evaluated in assays with A549 cells and hen egg chorioallantoic membrane models. This PhD project is conceived within the research line of the Fapesp 2014/50947-7.