Sistemas híbridos formados por nanobastões de ouro e porfirinas: fotossensibilizadores promissores para terapia fotodinâmica

Abstract

Gold nanostructures, spheres and rods, were synthesized to form a hybrid system with porphyrin H2TM4PyP(OTs)4 (POR) for application in photodynamic therapy (PDT) using light in the visible and near UV (UVA) spectral region. Electron Paramagnetic Resonance (EPR) experiments combined with the spin trapping technique were used to detect reactive oxygen species (ROS) and to evaluate the efficiency of these new hybrids as photosensitizers (FS). Our results show that the hybrid system composed of gold nanorods (AuNR) and POR is much more efficient in the generation of singlet oxygen (1O2) than its isolated components. This significant improvement in the efficiency of the process of 1O2 generation under visible light is explained by a synergistic effect between AuNR and porphyrin, where a rapid transfer of energy from the gold nanorods to the porphyrin produces a large amount of 1O2 followed by its conversion into hydroxyl radicals. The mechanism of ROS generation was investigated using different spin traps and suppressors for reactive oxygen species. On the other hand, spherical gold nanoparticles (AuNP) did not present synergistic effect when in the hybrid systems. This synergetic effect present in the hybrid of POR/AuNR is attributed to an increase of the local electric field near the surface of the anisotropic nanorods in comparison to the spherical AuNP, when irradiated with visible light. Under UVA light, the mechanism of singlet oxygen generation, in addition to energy transfer, involves the excitation of POR and charge transfer of its excited states to molecular oxygen, leading to the formation of O2-¿ and its dismutation into H2O2 which in aqueous solution and at basic pH produces singlet oxygen. The POR/AuNR hybrid system was also studied as a sensitizer in a methodology that combines radiotherapy and PDT. Ionizing radiation (gamma rays, ~ MeV) was used to validate the amplification model of ROS generation of in the presence of nanostructures with high atomic number (Z). Our results show that under gamma rays the dominant effect is the radiolysis of the water mainly forming OH¿ radicals, without apparent improvement by the Au nanostructures. On the other hand, porphyrin POR is capable of generating singlet oxygen under gamma rays, thus showing itself as a possible radiosensitizer (RS).