Photothermolysis of lymphatic endothelial cells by gold nanoshell-mediated hyperthermia.
Tumor-associated lymphatics and lymphangiogenesis have been shown to play important roles in promoting tumor growth and metastasis. However, the lymphatic system has received much less attention as a target of intervention in cancer treatment compared to the blood vascular system. In this study, we explored the feasibility of photothermal therapy targeting the lymphatic system as a strategy for inhibiting lymphatics-mediated tumor metastasis. Specifically, photothermolysis of lymphatic endothelial cells (LECs) via gold nanoshell-mediated hyperthermia was investigated. Near-Infrared-absorbing Au nanoshells (AuNSs) were synthesized and used as the photothermal coupling agent. After 24-hr incubation, significant amount of the AuNSs were taken up by murine simian virus lymphatic endothelial cells with minimal cytotoxicity. Thermally-induced injury to LECs was found to occur above a threshold temperature of 46 degrees C. Preliminary data also suggested apoptosis as the mechanism of thermally-induced cell death in this temperature range. In a proof-of-concept experiment, AuNS-mediated photothermal heating was found to induce cell death in statistically higher percent of LECs incubated with AuNSs after 15-min laser irradiation compared to the controls. We believed that the findings in this study represent the first step in developing AuNS-mediated photothermal therapy as a potential strategy to disrupt tumor-associated lymphatics.
Kui
K
Chen
Israel
I
Soto
W Todd
WT
Monroe
J Steven
JS
Alexander
D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D006046:Gold / Q000737:chemistry* / Q000627:therapeutic use*; D006979:Hyperthermia, Induced / Q000379:methods*; D008027:Light; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000528:radiation effects*; D051379:Mice; D010789:Phototherapy / Q000379:methods*; D011829:Radiation Dosage
D006046:Gold