期刊
BIOCONJUGATE CHEMISTRY
卷 22, 期 2, 页码 235-243出版社
AMER CHEMICAL SOC
DOI: 10.1021/bc100374p
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资金
- U.S. EPA-Science to Achieve Results (STAR) program [R831712]
- National Science and Engineering Research Council of Canada (NSERC)
- NSERC/CIHR
- NSERC CREATE Canadian Astrobiology Training Program
- EPA [909011, R831712] Funding Source: Federal RePORTER
Ultrasmall (mean diameter, 2.7 nm) gold nanoparticles conjugated to doxorubicin (Au-Dox) are up to 20-fold more cytotoxic to B16 melanoma cells than the equivalent concentration of doxorubicin alone, and act up to six times more quickly. Ultrasmall Au-Dox enters the cell endocytic vesicles and is also seen free in the cytoplasm and nuclei. This is in distinct contrast to larger particles reported in previous studies, which are excluded from the nucleus and which show no increased toxicity over Dox alone. Cell death with Au-Dox is confirmed to be apoptotic by TUNEL staining and ultrastructural examination using transmission electron microscopy. To further explore the mechanism of action, two other cell lines were examined: He La cells which are highly sensitive to Dox, and He La cells overexpressing Bcl-2 which show impaired apoptosis and Dox resistance. Interestingly, the Dox-sensitive cells show a slightly decreased sensitivity to Au-Dox relative to Dox alone, whereas the Dox-resistant cells are not resistant to Au-Dox These results have implications for the design of chemotherapeutic nanoparticles, suggesting that it is possible to selectively target apoptosis-resistant cancer cells while at the same time reducing cytotoxicity to normal cells.
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