Toxicity study of gold nanoparticle-doxorubicin conjugates: size-dependency and cellular location

• Main Author: 李宗翰
• Other Authors: 黃國華
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/24395654858214324380

碩士 === 國立交通大學 === 材料科學與工程學系奈米科技碩博士班 === 100 === The aim of this study is to explore possible toxicity reducing effect of gold nanoparticle (GNP) as drug carrier bringing doxorubicin (DOX) into cells and study the molecular mechanism of reducing effects. 16-mercaptohexadecanoic acid (MHA) was first bound to GNP and served as cross-linker. The GNP-MHA conjugate reacted with DOX to generate GNP-DOX conjugate. GNPs ranged from 5-nm to 50-nm. The efficiency of chemical reaction was monitored by UV-visible. The conjugates were purified through serial dialysis. Free DOX was applied as positive control. PA-1 cells was cultured for 48 hours and incubated with free DOX, 5-nm GNP-DOX, 8-nm GNP- DOX, 12-nm GNP- DOX, 17-nm GNP- DOX, 37-nm GNP- DOX, and 50-nm GNP -DOX. In addition, GNPs of various diameters were incorporated into free DOX to serve as control. All of GNP-DOX conjugates were reduced toxicity. Cellular locations of GNP-DOX conjugates indicated that the reducing effect might be due to GNPs-DOX conjugates translocate into nucleus difficultly. Increased nuclear localization of p53 and caspase-3 was observed in cells exposed to free DOX and GNP-DOX. The result indicate that free DOX and GNP-DOX induce cell death through apoptosis.