RESUMO
The development of effective polymer-based nanocarriers which are able to target diseased tissues still remains a great challenge in current research. Dendritic polyglycerols have emerged as novel polymeric scaffolds that have demonstrated a great potential for diverse biomedical applications. These architectures have already proven their usefulness in therapeutic approaches related to multivalency, given by the synergy between the nanosized dimensions combined with the high density of functional groups. However, a continuous effort is necessary to modify and tailor polyglycerol architectures to fit the future demands of biomedical applications. The present work deals with the development of a general synthetic strategy that allows the linkage of low molecular weight dendritic polyglycerols to fluorescent dyes and cell targeting ligands. The receptor mediated cellular uptake of the polyglycerol conjugates highlight their potential to acts as new targeted nanocarriers that should be able to decrease non-specific cellular uptake.
Assuntos
Dendrímeros/administração & dosagem , Glicerol/administração & dosagem , Terapia de Alvo Molecular/métodos , Polímeros/administração & dosagem , Receptores de Superfície Celular/química , Dendrímeros/química , Dendrímeros/farmacocinética , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Glicerol/química , Glicerol/farmacocinética , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/farmacocinética , Humanos , Maleimidas/administração & dosagem , Maleimidas/síntese química , Maleimidas/química , Peso Molecular , Nanoconjugados/química , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Polímeros/química , Polímeros/farmacocinética , Receptores de Superfície Celular/metabolismo , Distribuição Tecidual , Células Tumorais CultivadasRESUMO
To study the mechanism of cellular internalization, hyperbranched polyether derivatives consisting of amino-bearing hyperbranched polyglycerols (HPGs) of varied molecular mass and size range are designed and synthesized. HPGs were further fluorescently labelled by conjugating maleimido indocarbocyanine dye (ICC-mal). The conjugates are characterized by UV-vis spectroscopy, fluorescence profile, zeta potential, and dynamic light scattering. The uptake mechanism is studied by fluorescence-activated cell sorting (FACS) analysis, fluorescence spectroscopy, and confocal microscopy with human lung cancer cells A549, human epidermoid carcinoma cells A431, and human umbilical vein endothelial cells (HUVEC) cells. For the first time, the results suggest that the higher-molecular-weight HPGs (40-870 kDa) predominantly accumulate in the cytoplasm much better than their low-molecular-weight counterparts (2-20 kDa). The HPG nanocarriers discussed here have many biomedical implications, particularly for delivering drugs to the targeted site.