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Evaluation of the potential of transferrin-functionalized liposomes for docetaxel delivery for the treatment of prostate cancer

Grant number: 18/26422-2
Support Opportunities:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): March 18, 2019
Effective date (End): July 03, 2019
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Marlus Chorilli
Grantee:Mariza Aires Fernandes
Supervisor: Maria Jose Santos-Martinez
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Research place: Trinity College Dublin, Ireland  
Associated to the scholarship:17/25190-8 - Evaluation of the potential of transferrin-functionalized liposomes for docetaxel delivery in the treatment of prostate cancer, BP.MS

Abstract

Prostate cancer (PC) is the most common malignant urologic neoplasm and the second leading cause of cancer mortality in the world. Treatment is initiated through surgical interventions covering radical prostatectomy, followed by active surveillance, radiotherapy, as well as therapies involving androgen deprivation and immunotherapies. Chemotherapy is also widely used and recent studies have demonstrated remarkable control of PC growth using docetaxel (DTX), which acts to inhibit cell proliferation from sustained mitotic block during cell cycle metaphase / anaphase, which promotes the polymerization of stable microtubules and prevents cell division. However, DTX has side effects associated with toxicity of both the drug and the formulation, Taxotere®, in addition to rapid systemic clearance. As a result, the development of nanotechnology drug delivery systems, such as liposomes, has been promising for the treatment of prostate cancer because of the multiple favorable characteristics of these nanosystems, such as biocompatibility and biodegradability. One attractive approach to increase specificity and reduce side-effects is the surface modification of liposomes with specific ligands of the regulated receptors on the surfaces of tumor cells, such as transferrin receptors, which are overexpressed in prostate tumor cells. Liposomes formed by a mixture of lipids, conjugated with transferrin and loaded with DTX forming closed structures in simple concentric lipid bilayers. In this context, this project aims to evaluate the action of docetaxel carried by functionalized liposomes on tumor growth during the research stage at Trinity College Dublin using a prostate cancer cells, PC-3 that show overexpression of TfR and LNCaP, without TfR expression and comparation with healthy lines through the MTT assay. Evaluation of uptake of liposomes in prostate cancer cell lines and healthy cells by flow cytometry and confocal microscopy. Interactions between transferrin receptors and liposomes-transferrin conjugated will be evaluated using the commercially available quartz crystal microbalance with dissipation (QCM-D), which would allow a more detailed study on the action of docetaxel incorporated or not on conjugated liposomes-transferrin in tumor growth. (AU)

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Scientific publications
(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)
FERNANDES, MARIZA AIRES; ELOY, JOSIMAR O.; LUIZ, MARCELA TAVARES; RAMOS JUNIOR, SERGIO LUIZ; BORGES, JULIO CESAR; DE LA FUENTE, LAURA RODRIGUEZ; LUIS, CLARA ORTEGA-DE SAN; MARCHETTI, JULIANA MALDONADO; SANTOS-MARTINEZ, MARIA J.; CHORILLI, MARLUS. Transferrin-functionalized liposomes for docetaxel delivery to prostate cancer cells. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 611, . (17/25190-8, 14/50928-2, 18/26422-2)
AIRES-FERNANDES, MARIZA; ELOY, JOSIMAR O.; VICTORELLI, FRANCESCA DAMIANI; FERREIRA, PAULA SCANAVEZ; PIRONI, ANDRESSA MARIA; CHORILLI, MARLUS. Reversed-phase high-performance liquid chromatography: A fast and efficient analytical method to quantify docetaxel-loaded pegylated liposomes in release study. JOURNAL OF SEPARATION SCIENCE, v. 44, n. 21, . (18/26422-2, 17/25190-8, 14/50928-2)

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