Curcumin encapsulation in folate-functionalized bioMOF-100: development and evaluation of its potential in the treatment of breast cancer

Author(s)

Renata Carolina Alves

• Document type: Doctoral Thesis
• Press: Araraquara. 0000-00-00.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2021-11-12
• Advisor: Marlus Chorilli; Regina Célia Galvão Frem

Abstract

Cancer is a group of diseases that have in common the disordered growth of cells, resulting in the formation of new tissue called a malignant tumor. Breast cancer is the most incident and the most frequent cause of cancer death in women, representing the fifth leading cause of cancer death overall. Triple negative breast tumors, which do not have the traditional breast cancer markers, are considered the most aggressive and do not have specific therapy, being used conventional chemotherapy, associated with several side effects and low specificity. In order to try to improve these limitations of traditional therapy, there is a growing search for the development of new treatments for breast cancer, using, for example, drug delivery systems. Among the various systems studied, Biocompatible Metal Organic Frameworks (bioMOFs), that is, coordination polymers, can be promising and attractive for drug incorporation and release due to their relatively high surface area and pore sizes, intrinsic biodegradability and possibility of functionalization post-synthesis. Within this context, the objective of this thesis was to develop two new drug carrier systems (RCA and bioMOF-101) containing incorporated curcumin, whose surface of these materials was coated with folic acid molecules, in order to promote the targeting of these systems to the region tumor. Both RCA and bioMOF-101 carrier systems were synthesized and characterized using various characterization techniques, such as: infrared vibrational spectroscopy (FTIR), high resolution electron microscopy (FEG-SEM), powder X-ray diffraction (PXRD), thermal analysis (TG-DSC), polarized light optical microscopy and elemental analysis. After the characterizations, both materials were submitted to drug encapsulation tests, whose encapsulation efficiencies were 32.80% for CCM@RCA-1D and 99.42% for CCM@bioMOF-101-1D. From the 1H nuclear magnetic resonance (NMR) spectroscopy technique, it was possible to verify the appearance of signals referring to folic acid, suggesting success in the functionalization of these matrices. The materials with and without folic acid were submitted to drug release tests at dependent pH. With these tests it was possible to verify that both matrices presented higher release rates in acidic pH. In vitro tests such as cell viability and type of cell death were evaluated in both series of compounds (CCM@RCA-1D, CCM@RCA-1D/FA, CCM@bioMOF-101-1D and CCM@bioMOF-101-1D /FA) in breast tumor cell lines (MCF-7, 4T1, MDA-MB-231) and normal cell line (NHI/3T3). The results revealed a low toxicity of the materials and cell death by late apoptosis. In vivo studies were performed with the compounds CCM@bioMOF-101-1D and CCM@bioMOF-101-1D/FA and despite not showing a reduction in the tumor region, the compound CCM@bioMOF-101-1D/FA revealed a reduction in alveolar volume, which is an indication of its effectiveness against the tested model. Thus, these results indicate that the studied matrices can be promising carriers in the treatment of breast cancer. (AU)

• FAPESP's process: 17/26065-2 - Encapsulation of curcumin in BioMOF-100 functionalized with folate: development and evaluation of potential in the treatment of Breast Cancer
• Grantee: Renata Carolina Alves
• Support Opportunities: Scholarships in Brazil - Doctorate