Differential internalization of amphotericin B--conjugated nanoparticles in human cells and the expression of heat shock protein 70.

Abstract:

:Although a variety of nanoparticles (NPs) functionalized with amphotericin B, an antifungal agent widely used in the clinic, have been studied in the last years their cytotoxicity profile remains elusive. Here we show that human endothelial cells take up high amounts of silica nanoparticles (SNPs) conjugated with amphotericin B (AmB) (SNP-AmB) (65.4 ± 12.4 pg of Si per cell) through macropinocytosis while human fibroblasts internalize relatively low amounts (2.3 ± 0.4 pg of Si per cell) because of their low capacity for macropinocytosis. We further show that concentrations of SNP-AmB and SNP up to 400 μg/mL do not substantially affect fibroblasts. In contrast, endothelial cells are sensitive to low concentrations of NPs (above 10 μg/mL), in particular to SNP-AmB. This is because of their capacity to internalize high concentration of NPs and high sensitivity of their membrane to the effects of AmB. Low-moderate concentrations of SNP-AmB (up to 100 μg/mL) induce the production of reactive oxygen species (ROS), LDH release, high expression of pro-inflammatory cytokines and chemokines (IL-8, IL-6, G-CSF, CCL4, IL-1β and CSF2) and high expression of heat shock proteins (HSPs) at gene and protein levels. High concentrations of SNP-AmB (above 100 μg/mL) disturb membrane integrity and kill rapidly human cells (60% after 5 h). This effect is higher in SNP-AmB than in SNP.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Paulo CS,Lino MM,Matos AA,Ferreira LS

doi

10.1016/j.biomaterials.2013.03.048

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

5281-93

issue

21

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(13)00358-X

journal_volume

34

pub_type

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