Banca de QUALIFICAÇÃO: VICTÓRIA LAYSNA DOS ANJOS SANTOS

DEVELOPMENT OF POLYMER NANOPARTICLES FOR USE AS ANTINEOPLASTIC THERANOSTIC AGENTS.

Naphtoazoles. Naphthoimidazole. Naphthoxazole. Polymeric nanoparticles. Antineoplastic theranostics.

Cancer has high incidence and mortality rates associated with its occurrence. Currently, antineoplastic chemotherapy and its diagnosis have limitations, making it attractive to develop more effective agents. Among the strategies used, there is a theranostic approach, characterized by the union of therapy and diagnostic techniques in a single system. Naphthoazoles are promising candidates to act as theranostic agents, since they have high antineoplastic activity as well as the ability to emit fluorescence. Therefore, the development of polymeric nanoparticles containing naphthoazoles derived from -lapachone was proposed to be evaluated as anticancer and fluorescent nanotheranostics. Naphthoazoles were synthesized from the Debus-Radziszewski occurrence, using a -lapachone as a structural framework. Four naphthoazoles were found, named two naphthoimidazoles (IM3 and IM4) and two naphthoxazoles (OX4 and OX5). Naphthoazoles were obtained in yields of 25.4 and 43.9% and had their structures confirmed by Nuclear Magnetic Resonance (NMR) and Mass Spectroscopy (MS). The physicochemical and thermal characterization of naphthoazoles was carried out using infrared analysis (FT-IR), X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) and Thermogravimetry analyzes coupled with Differential Thermal Analysis (DTA). The findings proved the thermal stability of the synthesized naphthoazoles. Tests were also carried out to develop the HPLC-DAD quantification method and solubility tests. The synthesized naphthoazoles were also evaluated regarding their potential application as components of anticancer nanotheranostics, where it was proven that naphthoimidazole IM4 has greater applicability as a therapeutic component, while naphthoxazoles presented more interesting photophysical properties. Once synthesized and characterized, naphthoazoles are nanocarried into polymeric nanoparticles (NPs) based on polyethylene glycol (PEG) and poly(-caprolactone) (PCL). Finally, the nanotheranostics produced will be evaluated as anticancer and fluorescent nanotheranostics.