作者: Kevin Ho , Cristobal Morfin , Katarzyna Slowinska
DOI: 10.3390/MOLECULES24040676
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摘要: The in vitro efficacy of cancer prodrugs varies significantly between malignant cell lines. most commonly identified problems relate to delivery: uptake mechanism, endosomal entrapment, and drug release. Here we present the study collagen/cell penetrating hybrid (COL/CPP) peptide carriers intended deliver paclitaxel hypopharyngeal carcinoma (FaDu) cells. Confocal microscopy imaging revealed surprising response FaDu COL/CPP comparison previously studied lines: peptides that carry both COL CPP domain adsorb on surface. While was design facilitate cellular uptake, case cells, it also induced detrimental interactions with membrane. Despite surface adsorption, colocalization markers EEA1 LAMP1 reveals is internalized via pathway, are able escape before lysosome formation release paclitaxel. Therefore, main obstacle for delivery cells appears be related properties. This behavior seems specific could linked reported overexpression T5, heparanase splice variants produces protein lacking enzymatic activity heparanase. results increased concentration HSPG surface, possibly creates a barrier highly charged COL/CPP.