Dendrimers: the fluorination approach

• Main Author: Orfãos, Lydia Nadége Abreu dos
• Publication Date: 2020
• Format: Master thesis
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10400.13/3011
• topic: Dendrimers; Nanoquímica; Nanomateriais; Dendrimers; Nanochemistry; Nanomaterials; Fluorination; Nanochemistry and Nanomaterials; .; Faculdade de Ciências Exatas e da Engenharia

The developmentsin materialsscience have provided new approaches for the detection, diagnosis and treatment of several diseases. Dendrimers have been intensively studied for their unique properties as probes and drug/gene delivery vehicles, mainly due to their multivalency and possibility of surface functionalization with a wide variety of compounds. This thesis aimed at the functionalization of generation four amine-terminated poly(amidoamine) (PAMAMG4-NH2) dendrimers with the compound 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid (TFHBA) for the obtention of new gene delivery vectors having increased transfection efficiency and high cytocompatibility, taking advantage of the “fluorine effect”. The traceability potential of this system using 19F-TFHBA in nuclear magnetic resonance, although not studied in the present thesis, was also a significant reason for the developed work. The functionalization of the PAMAMG4-NH2 dendrimer was performed with two functionalization degrees using TFHBA/dendrimer ratios of 32.5 and 64.5. A control using 4-hydroxybenzoic acid (HBA), the non-fluorinated counterpart of TFHBA, was also used at the same functionalization degrees. Several techniques were applied for the characterization of the synthesized materials, such as Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared (FTIR), Ultraviolet/Visible (UV/Vis), and fluorescence spectroscopies, as well as Dynamic Light Scattering (DLS) and Electrophoretic Light Scattering (ELS), to confirm the success of the conjugation. Biological studies of the prepared compounds were performed, too, namely cytotoxicity, pDNA condensation and charge neutralization capability, and transfection efficiency. The functionalization of PAMAMG4-NH2 dendrimers with TFHBA and HBA at both functionalization degrees was achieved successfully. Compared to pristine PAMAMG4-NH2, the functionalized dendrimers presented lower cytotoxicity, similar pDNA condensation ability, and better transfection efficiency in HEK293T cells. Based on the obtained data, no significant differences were observed between the TFHBA and HBA functionalized dendrimers as transfection agents.