Development of nanotechnology tools designed to induce death in prostate cancer cells

Author(s)

Marcelo Bispo de Jesus

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2009-12-02

Examining board members

Eneida de Paula; Pietro Ciancaglini; Nelson Eduardo Duran Caballero; Francisco Benedito Teixeira Pessine; Sergio Antonio Fernandes

• Advisor: Eneida de Paula; Carmen Veríssima Ferreira

Abstract

Even after more than half a century of research and development in chemotherapy, cancer remains one of the most difficult diseases to treat. Among the cancer types, prostate adenocarcinome is the most incident in male. The insufficient advances attained so far in cancer treatment led us to explore two strategies designed to obstruct proliferation of prostate cancer cells. At the first, a drug delivery system based on cyclodextrins and aimed to improve the bioavailability of riboflavin (a vitamin able to induce apoptosis in tumor cells) was prepared, characterized and tested. The second strategy consisted in the development of a gene delivery system based on solid lipid nanoparticles for future transfer of tumor suppressor genes able to induce death of prostate cancer cells. The first part of this thesis comprises the physico-chemical characterization of beta (b-CD) and hydroxypropyl beta (HP-b-CD) cyclodextrins complexes with riboflavin, followed by evaluation of their toxicity against prostate cancer cells. Riboflavin complexation with cyclodextrins increased the solubility of this vitamin and its effectiveness against prostate cancer cells growth. However, the molecular interaction of riboflavin with either b-CD or HP-b-CD was unusual, as evidenced by nuclear magnetic resonance (Overhauser Nuclear Effect) experiments. In the second part solid lipid nanoparticles of ca. 100 nm and composed of stearic acid, 1,2-dioleoyl-3-trimethylammonium-propane and Pluronic F68 (with or without 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) were prepared. Stability (evaluated by size and Zeta potential of the nanoparticles) was quite good during a 140 days storage period. The nanoparticles were able to protect genetic material against DNase action and showed a transfection capacity comparable to that of Lipofectamine 2000®, a commercially available gene carrier. Keywords: Prostate - Cancer; Riboflavin; Cyclodextrins; Solid lipid nanoparticles; Gene transfer techniques. (AU)

• FAPESP's process: 06/03838-1 - Use of nanotechnology tools designed to induce death in prostate cancer cells
• Grantee: Marcelo Bispo de Jesus
• Support Opportunities: Scholarships in Brazil - Doctorate