Desenvolvimento de sistema troiano de entrega de fármacos: nanopartículas biencapsuladas com dacarbazina e ftalocianina de zinco radiomarcadas com tecnécio99m como nanoteranósticos para o melanoma metastático

Abstract

Melanoma is an invasive and very aggressive skin cancer due to its resistance to various drugs, which results in low patient survival, being responsible for 80% of deaths from skin cancers each year. Its pathogenesis is not yet fully elucidated, which also justifies the high mortality rate, added to the lack of effective treatment alternatives and limitations in its diagnosis. It is necessary to test new treatment approaches to improve therapeutic efficacy and reduce the side effects of conventional treatments. In current therapy, Dacarbazine (DTIC) is the only FDA-approved antineoplastic agent for melnaoma, however its responsive rate is low, making the prognosis poor. In order to circumvent this critical scenario, the early and adequate diagnosis of metastatic melanoma is the main key to potential survival, therefore, the use of radionuclides as molecular markers has been highlighted within medicine. And, through the use of biocompatible nanostructures, it is possible to produce nanopharmaceuticals capable of acting with a high performance, especially regarding their penetrability and specific targeting, also achieving robust therapeutic results creating a teragnostic structure. What allowed to improve therapeutic alternatives such as the use of photosensitizing agents in photodynamic therapy, through structural change and the functionalization of nanomaterials, capable of making stable associations with various drugs or molecules, which results in an optimization of the theragnosis process. In the present work, a nanoparticle drug delivery system (NP) was developed that transports both chemotherapeutic drugs (Dacarbazine) and photosensitizing agents (zinc phthalocyanine) using MV3 melanoma cells as a model. In vitro cell viability studies demonstrate that therapeutic efficacy is dose dependent. The in vivo results demonstrate that the drug load affects the biodistribution of PN formulations. The low accumulation of NPs in the stomach, heart, brain and kidneys suggests that the common side effects of dacarbazine can be reduced. This paper reports on a robust formulation of nanoparticles with the aim of leveraging the synergistic effects of chemotherapy and photodynamic therapies to potentially suppress the likelihood of drug resistance and reduce the side effects associated with dacarbazine.