RESUMO
We demonstrate here that the genetic incorporation of the fusogenic peptide HA2 into a CXCR4-targeted protein nanoparticle dramatically reduces the specificity of the interaction between nanoparticles and cell receptors, a factor to be considered when designing tumor-homing drug vehicles displaying endosomal-escape agents. The loss of specificity is concomitant with enhanced cell penetrability.
Assuntos
Hemaglutininas Virais/química , Nanopartículas/química , Receptores CXCR4/química , Receptores de Superfície Celular/química , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Endossomos/química , Endossomos/metabolismo , Fluorescência , Células HeLa , Hemaglutininas Virais/genética , Hemaglutininas Virais/metabolismo , Humanos , Nanopartículas/metabolismo , Receptores CXCR4/metabolismo , Receptores de Superfície Celular/metabolismo , Células Tumorais CultivadasRESUMO
Pesticides (organochlorines-OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals are toxic to fish and may be taken in through gills, skin and contaminated foods. Here we measure concentrations of OC, PAH and heavy metals, and their effects in the eel Anguilla anguilla from three locations in the Camargue Reserve in southern France. The Camargue Biosphere Reserve is the largest coastal wetland in Western Europe, and A. anguilla is a common predator at the top of the food chain. Livers and spleens were analyzed for histopathological, chemical and organo-somatic (HSI and SSI) effects. Gill, liver and spleen samples were collected for histopathological studies. Livers and muscles were sampled for metabolic parameters and persistent organic pollutant analysis. Total lipids were estimated by spectrophotometry and lipid-free residues were used in protein and glycogen analysis. OC pesticides were extracted from lipids of muscles and livers, analyzed by gas chromatography, and PAH from bile were analyzed by fixed wavelength fluorescence spectrofluorimetry. Heavy metals were measured by inductively coupled plasma with optical or with mass spectrometers. High concentrations of contaminants were found in eel tissues. La Capelière had the greatest OC and PAH concentrations; unexpected lesions in gills, livers and spleens were more common at the other sites. Liver and spleen tumors and lipidosis in livers were associated with chronic, and gill lesions with acute exposure. High pesticide and PAH concentrations and lesions in eels from the Camargue reserve demonstrate the contamination of the area. A more complete study in the Camargue reserve is necessary to better understand the impact on wildlife and humans. Also, this study suggests that eel biology must be better understood before continued use of this species as a biomonitor of polluted areas.