Síntese e caracterização de BioMOFs (Biocompatible Metal-Organic Frameworks) de Zn(II) para aplicação em drug delivery de metalofármacos anticancerígenos

• Autor(a) principal: Armando, Renan Augusto Marson
• Data de Publicação: 2022
• Tipo de documento: Trabalho de conclusão de curso
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/216625
• topic: MOFs; Sistema de liberação de fármacos (SLF); Fármacos anticancerígenos; Metalofármacos

One of the greatest bottlenecks in modern medicine has been the development and use of biocompatible carriers that assure efficient drug delivery in the body. Most of the existing carriers have shown some drawbacks like poor loading and rapid drug release with a "burst" effect. In this context, a subclass of coordination polymers, known as Metal-Organic Frameworks (MOFs), has drawn the attention of researchers across the world: the unique physical properties of MOFs make them exceptional materials for drug delivery systems (DDS). Here, we have synthesized and characterized a non-toxic Zn-based MOF, designated bio-MOF-1, by using 4,4'-biphenyldicarboxylic acid and adenine as linkers. The microcrystalline porous material presented great loading capacity (0.340 g g -1) for the antitumoral metallodrug Ru-90 [cis-[Ru(bpy)2(NO2)(solv)](PF6)]. The release of Ru-90 from the bio-MOF-1 matrix is depending on pH, and therefore, this material is a promising candidate for anticancer drug delivery. The fitting of kinetic equation models showed that the mechanism of Ru-90 release from bio- MOF-1 is adjusted by the Korsmeyer-Peppas model for the system at pH 5,0 and pH 7,4; the plots displayed high linearity and correlation coefficient values (R2 ) greater than 0.96. The n values were under 0.45 (Korsmeyer-Peppas model), which suggested the quasi Fickian model for the transport mechanism. In fact, the kinetic study results showed that bio-MOF-1 delivers the anticancer complex Ru-90 mostly through a diffusive mechanism. The in vitro cytotoxicity results demonstrated that Ru-90 occlusion facilitated its access and increased its availability in the cells A395 (tumoral) and L929 (non-tumoral). Moreover, microcrystalline particles of bio-MOF-1, here named Zn_HAc, Zn_pyd and Zn_pydmicro, were obtained by microwaves-assisted techniques and the addition of coordination modulators. The use of acetic acid as a modulator decreased slightly the size of particles when compared to the conventional solvothermal route. In conclusion, depending on the type of modulator (acetic acid or pyridine) as well as the synthetic route (conventional solvothermal or microwave-assisted), we were capable to obtain different morphologies (rods, spheres, and clusters).