Nuclear targeting of gold nanoparticles in cancer cells induces DNA damage, causing cytokinesis arrest and apoptosis.
By properly conjugating gold nanoparticles with specific peptides, we were successful in selectively transporting them to the nuclei of cancer cells. Confocal microscopy images of DNA double-strand breaks showed that localization of gold nanoparticles at the nucleus of a cancer cell damages the DNA. Gold nanoparticle dark-field imaging of live cells in real time revealed that the nuclear targeting of gold nanoparticles specifically induces cytokinesis arrest in cancer cells, where binucleate cell formation occurs after mitosis takes place. Flow cytometry results indicated that the failure to complete cell division led to programmed cell death (apoptosis) in cancer cells. These results show that gold nanoparticles localized at the nuclei of cancer cells have important implications in understanding the interaction between nanomaterials and living systems.
Kang
Bin
B
Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, USA.
Mackey
Megan A
MA
El-Sayed
Mostafa A
MA
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048749:Cytokinesis / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006046:Gold / Q000032:analysis*; D006801:Humans; D053768:Metal Nanoparticles / Q000032:analysis*; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage* / Q000627:therapeutic use*
D009842:Oligopeptides; D010455:Peptides; D006046:Gold; C047981:arginyl-glycyl-aspartic acid