Toxicity of Nanomaterials and Mechanisms of Endocytic Pathways

[摘要] Engineered nanoparticles (NP) are small in size, large in surface area and can havedifferent types of coating and functionalization. In addition, there are other characteristicsof the NP such as unique chemical, mechanical, electrical, optical, and magneticproperties, as well as ability of tracking and quantification provide the possibility toutilize them in NP-based diagnosis or therapy. The potential for NP use incommercialized biomedical applications is increasing but the toxicity and biodistributionin biological systems is unknown. Since the 1990’s, a focus of NP research has been touncover the associations between NP interactions in vitro and in vivo. However, NPinteractions with skin has been limited. The goal of this research is to investigate theeffects of several types of NP of different sizes, charges, and surface coatings on skin, orin human epidermal keratinocytes (HEK). Quantum dots (QD) have received attentiondue to their fluorescent properties. The penetration and interaction of QD in skin and theeffect on HEK were studied. QD with different surface coatings remained in the stratumcorneum layers or in the outer root sheath of hair follicles of rat skin and porcine skin.However, QD showed an increase in penetration in the dermis of the abraded skin but nottape-stripped rat skin. HEK viability decreased and cytokine release increased with QD.QD were internalized by HEK and localized freely or in cytoplasmic vacuoles. Weinvestigated the interaction and uptake of carbon based NP such as multi-walled carbonnanotubes, amino acid derived single-walled carbon nanotubes, and fullerenefunctionalized peptides in HEK. The uptakes of NP were shown and the mechanism ofhow NP were incorporated into cells was also investigated. Carboxylic acid coated QD orfullerene peptides were utilized as targets to explore the endocytic mechanisms. Thesestudies suggested that general pathways such as caveolae/lipid rafts, as well as specificreceptors such as G protein coupled receptor and low density lipoprotein/scavengerreceptors can regulate NP uptake in cells.

[发布机构] University:North Carolina State University

[效力级别] toxicity

[关键词] endocytic pathways;toxicity;nanomaterial