Lipid nanoparticles as a Co-Delivery system for genes and drugs: development, cellular processing and biological activity in cancer cells

• Grant number: 12/01038-9
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): April 01, 2012
• Effective date (End): February 28, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Carmen Veríssima Ferreira
• Grantee: Marcelo Bispo de Jesus
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Even after significant advances in the treatment of breast cancer and prostate cancer, the treatment of these diseases still is a challenge. Nanomedicine emerges as a toolbox to assist the treatment and diagnosis of various diseases, including cancer. In addition, it allows us to combine the conventional therapy and promising therapies, such as gene therapy. It offers therapeutic effects that are not achieved by conventional therapy. However, the use of new technologies also brings new challenges, not only to the development of new nanodevices, but also to the study of the interaction of these nanomaterials with biological environment. This project aims to optimize the production of solid lipid nanoparticles (SLN), which are highly efficient for gene delivery into prostate cancer cells (PC3), for co-delivery of drugs and genes. Furthermore, test these SLNs as co-delivery systems into breast cancer cells (MCF-7). The gene for Phosphatase and tensin homolog (PTEN) protein was chosen to be delivered, once it is deleted in both prostate and breast cancers cells and its expression at critical levels can induce death in these cells. Mitoxantrone was the drug chosen once it has a good interaction with the SLN nanoparticles; and this formulation even at low concentrations of MTX were able to induce death in prostate cancer and breast cancer cells. The study of the mechanisms of internalization and intracellular trafficking of these nanoparticles can also reveal the mechanisms involved in the co-delivery of genes and drugs, which would be unprecedented in the literature. In addition, knowledge of these mechanisms will assist us in developing more efficient nanodevices.

Scientific publications

(5)

(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)

DE JESUS, MARCELO BISPO; RADAIC, ALLAN; ZUHORN, INGE S.; DE PAULA, ENEIDA. Microemulsion extrusion technique: a new method to produce lipid nanoparticles. JOURNAL OF NANOPARTICLE RESEARCH, v. 15, n. 10, SEP 3 2013. (12/01038-9, 09/13110-3)

SIPOLI, CAROLINE CASAGRANDE; RADAIC, ALLAN; SANTANA, NATHALIA; DE JESUS, MARCELO BISPO; DE LA TORRE, LUCIMARA GAZIOLA. Chitosan nanoparticles produced with the gradual temperature decrease technique for sustained gene delivery. Biochemical Engineering Journal, v. 103, p. 114-121, NOV 15 2015. (12/01038-9)

RADAIC, ALLAN; DE PAULA, ENEIDA; DE JESUS, MARCELO BISPO. Factorial Design and Development of Solid Lipid Nanoparticles (SLN) for Gene Delivery. Journal of Nanoscience and Nanotechnology, v. 15, n. 2, p. 1793-1800, FEB 2015. (12/01038-9, 09/13110-3)

PELIZZARO-ROCHA, KARIN JULIANE; DE JESUS, MARCELO BISPO; RUELA-DE-SOUSA, ROBERTA REGINA; NAKAMURA, CELSO VATARU; REIS, FABIANO SOUZA; DE FATIMA, ANGELO; FERREIRA-HALDER, CARMEN VERISSIMA. Calix[6]arene bypasses human pancreatic cancer aggressiveness: Downregulation of receptor tyrosine kinases and induction of cell death by reticulum stress and autophagy. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1833, n. 12, p. 2856-2865, DEC 2013. (12/01038-9)

DE JESUS, MARCELO B.; ZUHORN, INGE S.. Solid lipid nanoparticles as nucleic acid delivery system: Properties and molecular mechanisms. JOURNAL OF CONTROLLED RELEASE, v. 201, p. 1-13, MAR 10 2015. (12/01038-9)