RESUMO
It has been found that the self-assembly of nonfluorescent peptides can generate fluorescent peptide nanoparticles (f-PNPs) to perform multiple functions, including drug delivery and imaging and tracking therapeutic agents. Both pharmacologically inactive peptides and tumor-targeting peptides have been explored to construct biocompatible f-PNPs; however, the application of this technology in delivering antitumor peptides has never been reported. Herein, the self-assembly of an antitumor dipeptide, carnosine, into fluorescent carnosine nanoparticles (f-Car NPs) in the presence of zinc ions is demonstrated. The generated f-Car NPs exhibit fluorescence in the visible and near-infrared (NIR) ranges for fluorescence tracing in vitro and in vivo. On the other hand, the f-Car NPs minimize the contact between the dipeptide and the serum, which overcomes the dipeptide instability resulted from inefficient antitumor activity. In addition, the preparation of f-Car NPs does not introduce extra carrier materials, so the f-Car NPs exhibit biocompatibility to normal fibroblast cells in vitro and negligible toxicity against major organs in vivo. This study provides a new peptide drug delivery strategy with NIR fluorescence tracing ability.
Assuntos
Antineoplásicos/uso terapêutico , Carnosina/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Carnosina/química , Carnosina/efeitos da radiação , Carnosina/toxicidade , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Fluorometria/métodos , Humanos , Raios Infravermelhos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Camundongos Endogâmicos BALB C , Nanomedicina Teranóstica/métodos , Zinco/químicaRESUMO
After irradiation with 0.5 Mrad or higher doses, a radiation-induced ninhydrin-positive compounds was found in the muscle tissue of warm-blooded animals. In carp muscle another compound called X was formed. The origin of these two compounds was investigated. Irradiation of various amino acids and related compounds showed that substance Y is formed from the dipeptides carnosine and anserine, which are present in muscle tissue of warm-blooded animals unusually high concentrations. In carp muscle containing relatively high levels of histidine, but only low concentrations of anserine as the only dipeptide, histidine furnished compound X. This compound was found to be relatively stable in acid medium. After acid hydrolysis of irradiated carnosine solutions and of extracts of irradiation muscle tissue from warm-blooded animals, compound Y was no longer observed, but another compound appeared that was similar to X with regard to colour and migration properties during high-voltage electrophoresis and column chromatography.