RESUMO
Porphyrin derivatives accumulate selectively in cancer cells and are can be used as carriers of drugs. Until now, the substituents that bind to porphyrins (mainly at the meso-position) have been actively investigated, but the effect of the functional porphyrin positions (ß-, meso-position) on tumor accumulation has not been investigated. Therefore, we investigated the correlation between the functional position of substituents and the accumulation of porphyrins in cancer cells using cancer cells. We found that the meso-derivative showed higher accumulation in cancer cells than the ß-derivative, and porphyrins with less bulky substituent actively accumulate in cancer cells. When evaluating the intracellular distribution of porphyrin, we found that porphyrin was internalized by endocytosis and direct membrane permeation. As factors involved in these two permeation mechanisms, we evaluated the affinity between porphyrin-protein (endocytosis) and the permeability to the phospholipid bilayer membrane (direct membrane permeation). We found that the binding position of porphyrin affects the factors involved in the transmembrane permeation mechanisms and impacts the accumulation in cancer cells.
Assuntos
Endocitose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Porfirinas/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Humanos , Bicamadas Lipídicas/química , Células MCF-7 , Espectroscopia de Ressonância Magnética , Fosfolipídeos/química , Porfirinas/síntese química , Porfirinas/farmacologia , Espectrofotometria UltravioletaRESUMO
Porphyrin is accumulated in tumours due to its interaction with protein. Cancer therapy with porphyrin as a carrier molecule is attracting attention. Porphyrin displays two functional sites termed ß- and meso-positions. A correlation between the functional position on the porphyrin molecule and the ability to accumulate in cancer cells is observed in the present study. The accumulation of porphyrin derivatives was determined by measuring fluorescence intensity after incubation for 2 and 24 h. The accumulation of cancer cells depended on the position and length of functional groups. Estimated binding constants between porphyrin and bovine serum albumin suggest that the position of functional groups leads to changes in binding affinity and influences the accumulation of porphyrin derivatives in cancer cells.