Comparative cytotoxicity of gold-doxorubicin and InP-doxorubicin conjugates.
Direct comparisons of different types of nanoparticles for drug delivery have seldom been performed. In this study we compare the physical properties and cellular activity of doxorubicin (Dox) conjugates to gold nanoparticles (Au) and InP quantum dots of comparable diameter. Although the Au particles alone are non-toxic and InP is moderately toxic, Au-Dox is more effective than InP-Dox against the Dox-resistant B16 melanoma cell line. Light exposure does not augment the efficacy of InP-Dox, suggesting that conjugates are breaking down. Electron and confocal microscopy and atomic absorption spectroscopy reveal that over 60% of the Au-Dox conjugates reach the cell nucleus. In contrast, InP-Dox enters cell nuclei to a very limited extent, although liberated Dox from the conjugates does eventually reach the nucleus. These observations are attributed to faster Dox release from Au conjugates under endosomal conditions, greater aggregation of InP-Dox with cytoplasmic proteins, and adherence of InP to membranes. These findings have important implications for design of active drug-nanoparticle conjugates.
Department of Biomedical Engineering, McGill University, 3775 University Street, Montreal QC, H3A 2B4, Canada.
Xuan
X
Zhang
Hicham
H
Chibli
Dekun
D
Kong
Jay
J
Nadeau
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004357:Drug Synergism; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D007204:Indium / Q000008:administration & dosage* / Q000737:chemistry; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage*; D010720:Phosphines / Q000008:administration & dosage* / Q000737:chemistry
D053769:Nanocapsules; D010720:Phosphines; D007204:Indium; D006046:Gold; D004317:Doxorubicin; C090882:indium phosphide