Novos complexos micelares de metais de transição para aplicação na terapia dirigida contra o cancro

O cancro é a segunda causa de mortalidade a nível mundial. Um dos problemas nos tratamentos atuais de quimioterapia relaciona-se com os efeitos secundários causados pela falta de seletividade dos fármacos utilizados. Assim, um dos desafios atuais é o desenvolvimento de sistemas terapêuticos que permitam potenciar o efeito dos fármacos e diminuir os seus efeitos nocivos. Neste contexto, neste trabalho, foram sintetizados complexos de Fe, Co e Zn com fórmula geral [M(bipy-R)3]x+, a partir dos quais foi possível obter sistemas micelares formados in situ pela adição de um copolímero de PLA-b-PEG ou por introdução de macroligandos poliméricos anfifílicos. Os resultados mostram que as nanopartículas formadas apresentam tamanho e características adequadas para aplicações na terapia dirigida contra o cancro. Os resultados preliminares de citotoxicidade na linha tumoral humana da mama MDAMB231 indicam que todos os compostos estudados apresentam atividade citotóxica relevante, sendo os compostos micelares os mais promissores; Abstract: New micellar transition metals complexes for targeted therapy of cancer Cancer is the second leading cause of mortality worldwide. One problem in the current chemotherapy treatments is related to the severe side effects caused by the lack of selectivity of the drugs in clinical use. Thus, one of the current challenges is the development of new therapeutic systems that allow maximizing the effect of the drugs and reducing their harmful effects. In this context, several Fe, Co and Zn compounds of the general formula [M (bipy-R)3]x+ were synthesized in order to obtain micellar systems, either by in situ addition of a PLA-b-PEG copolymer or by introducing amphiphilic macroligands. The results show that the formed nanoparticles have size and characteristics suitable for applications in targeted therapy against cancer. Preliminary results of cytotoxicity in human breast cancer line MDAMB231 indicate that all the studied compounds show significant cytotoxic activity, being the micellar compounds the most promising agents.

NEW METAL-BASED MICELLES AS ANTICANCER AGENTS

Cancer is a leader cause of death worldwide. One of the problems associated with the current chemotherapeutic options is the noxious side effects caused by the lack of selectivity. In this frame, our research group has been committed to the development of a new Ru and Fe macrometallodrugs.[1] The data obtained so far shows that these compounds present an intrinsic selectivity towards cancer cells (relatively to healthy cells) due to the incorporation of polymeric ligands that promote a passive targeting through the cancer cell membrane. These results prompted us to the development of new macrometallodrugs bearing bioessential metals such as Fe, Zn and Co. We used a ‘M(bipy) 3 ’ scaffold (bipy = 2,2’-bipyridine derivatives) for the synthesis of the new compounds due to the promising cytotoxicity results observed for related compounds.[2] As polymeric ligands we have chosen the polylactide-co-polyethylene glycol amphiphilic copolymer that is able to self-assemble into micelles in water, keeping the metal center hidden, like a Trojan horse. We will present the synthesis and characterization of the new compounds and some preliminary data on their ability to form stable micelles (Figure 1).