RESUMO
The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/tratamento farmacológico , Estruturas Metalorgânicas/uso terapêutico , Porfirinas/uso terapêutico , Sorafenibe/uso terapêutico , Animais , Antineoplásicos/farmacologia , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Liberação Controlada de Fármacos , Humanos , Sistema de Sinalização das MAP Quinases , Nanomedicina , Fosforilação , Ratos , Ratos Sprague-DawleyRESUMO
Reactive oxygen species, contributing to oxidant-antioxidant imbalance, initiate damage to the airways cells, inflammatory processes, and further pathophysiological effects. Enhancing antioxidant properties is the main prophylactic and therapeutic challenge. In this work, a newly synthesized and biocompatible structure of the metal-biomolecule frameworks (MBioF) harnessing cystine as a linker and magnesium as metal nodes is presented. This structure provides crucial sulfhydryl groups of cysteine, with antioxidant activity, released stepwise in the site of delivery. We prove that once released, the compounds of MBioF increase the intracellular level of cysteine and total antioxidative capability of airway cells. Presented MBioF structures offer new perspectives for clinical applications as therapeutics or preventatives maintaining the antioxidant-oxidant balance.
