Synthesis of lipid nanocarriers for modulation of tumor and immunocompetent cells

• Grant number: 18/12670-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2019
• End date: July 31, 2021
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Valtencir Zucolotto
• Grantee: Edson José Comparetti
• 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

Cancer is the most recurrent chronic disease in the world. Human Hepatocellular Carcinoma (HCC) is the second type of Cancer with highest number of deaths in the world and their frequency of relapses and metastasis require the development of new diagnostic and therapeutic approaches. Neoplastic cells have the ability to evade immune surveillance, modulating tumor microenvironment, to favor tumor progression in the body. Nanocomposites can be used to prevent the expression of immunosuppressive proteins and cytokines, increasing the activity of the main mechanisms of cellular immunity. This project aims to develop a nanocarrier to transport immunomodulatory agents into Cancer and immunocompetent cells. Nanoparticles will be synthesized with lipids and proteins from plasma membrane of neoplastic cells to deliver a large amount of antigenic material to professional Antigen-Presenting Cells (APC). To establish a pro-inflammatory response, lipid nanoparticles will be incorporated with monophosphoryl lipid A and oligonucleotide sequence (siRNA or LNA) to silence a specific oncogene. Following, nanoparticles will be exposed to HCC cells, peripheral blood monocytes from healthy donors, Dendritic Cells (DCs) and macrophages generated in vitro. The nanocarriers will be tested for: a) nanoparticle internalization into cancer and immunocompetent cells; b) immunomodulatory activity, observing the expression of cell surface markers and cytokine production, and c) cytotoxicity of nanocarriers. Uptake will be analyzed by fluorescence microscopy and cytotoxicity by flow cytometry. We aim at increasing the immunogenicity of the tumor cell, upon positively modulating the action of the antigen-presenting cells (APCs). (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CORREIA, ABILENE RODRIGUES; SAMPAIO, ISABELLA; COMPARETTI, EDSON JOSE; VIEIRA, NIRTON CRISTI SILVA; ZUCOLOTTO, VALTENCIR. Detecting cancer cells with a highly sensitive LbL-based biosensor. Talanta, v. 233, OCT 1 2021. (18/12670-4, 18/07508-3)

ESTEVAO, BIANCA MARTINS; COMPARETTI, EDSON JOSE; RISSI, NATHALIA CRISTINA; ZUCOLOTTO, VALTENCIR. Anti-GPC1-modified mesoporous silica nanoparticles as nanocarriers for combination therapy and targeting of PANC-1 cells. MATERIALS ADVANCES, v. 2, n. 15, JUN 2021. (18/12670-4, 17/22056-9, 20/00124-5)

RISSI, NATHALIA CRISTINA; COMPARETTI, EDSON J.; ESTEVAO, BIANCA MARTINS; MASTELARO, VALMOR ROBERTO; ZUCOLOTTO, VALTENCIR. Doped Plasmonic Zinc Oxide Nanoparticles with Near-Infrared Absorption for Antitumor Activity. ACS APPLIED NANO MATERIALS, v. 4, n. 9, p. 9779-9789, SEP 24 2021. (18/12670-4, 17/22056-9, 20/00124-5)

COMPARETTI, EDSON J.; LINS, PAULA M. P.; QUITIBA, JOAO V. B.; ZUCOLOTTO, VALTENCIR. Cancer cell membrane-derived nanoparticles improve the activity of gemcitabine and paclitaxel on pancreatic cancer cells and coordinate immunoregulatory properties on professional antigen-presenting cells. MATERIALS ADVANCES, v. 1, n. 6, p. 1775-1787, SEP 1 2020. (18/12670-4)

COMPARETTI, EDSON J.; LINS, PAULA M. P.; QUITIBA, JOAO; ZUCOLOTTO, VALTENCIR. Cancer cell membrane-derived nanoparticles block the expression of immune checkpoint proteins on cancer cells and coordinate modulatory activity on immunosuppressive macrophages. Journal of Biomedical Materials Research Part A, v. 110, n. 8, p. 13-pg., 2022-04-05. (18/12670-4, 20/00124-5, 14/50947-7)

CORREIA, ABILENE RODRIGUES; SAMPAIO, ISABELLA; COMPARETTI, EDSON JOSE; SILVA VIEIRA, NIRTON CRISTI; ZUCOLOTTO, VALTENCIR. Optimized PAH/Folic acid layer-by-layer films as an electrochemical biosensor for the detection of folate receptors. BIOELECTROCHEMISTRY, v. 137, FEB 2021. (18/07508-3, 18/12670-4)

COMPARETTI, EDSON J.; FERREIRA, NATALIA N.; FERREIRA, LEONARDO M. B.; KANENO, RAMON; ZUCOLOTTO, VALTENCIR. Immunomodulatory properties of nanostructured systems for cancer therapy. Journal of Biomedical Materials Research Part A, v. 110, n. 5, p. 16-pg., 2022-01-19. (18/12670-4, 19/25645-0, 20/00124-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COMPARETTI, Edson José. Nanoengineerded cell membrane-based nanoparticles for tumor and immunocompetent cells modulation. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.