The potential use of the enhanced nonlinear properties of gold nanospheres in photothermal cancer therapy.
OBJECTIVE
Laser photothermal therapy (PTT) is practiced at the moment using short laser pulses. The use of plasmonic nanoparticles as contrast agents can decrease the laser energy by using the optical property of the nanoparticles and improve the tumor selectivity by the molecular probes on the particle surface. In this study, we aim at selective and efficient PTT by exploiting the nonlinear optical properties of aggregated spherical gold nanoparticles conjugated to anti-epidermal growth factor receptor (anti-EGFR) antibodies using short NIR laser pulses.


METHODS
Spherical gold nanoparticles are synthesized and conjugated to anti-EGFR antibodies to specifically target HSC oral cancer cells. The nanoparticles are characterized by micro-absorption spectra and dark field light scattering imaging. Photothermal destructions of control and nanoparticle treated cancer cells are carried out with a femtosecond Ti:Sapphire laser at 800 nm with a pulse duration of 100 femtoseconds and repetition rate of 1 kHz.


RESULTS
The laser power threshold for the photothermal destruction of cells after the nanoparticle treatment is found to be 20 times lower than that required to destroy the cells in the normal PTT, that is, without nanoparticles. The number of destroyed cells is quadratically dependent on the laser power. The number of dead cells shows a nonlinear dependence on the concentration of gold nanoparticles that are specifically targeted to cancer cells.


CONCLUSIONS
The energy threshold and selectivity of PTT can greatly benefit from the use of the plasmonic enhanced nonlinear optical processes of spherical gold nanoparticles conjugated to anti-EGFR antibodies. The quadratic dependence of the photothermal efficiency on the pulsed NIR laser power indicates a second harmonic generation or a two photon absorption process. The observed nonlinear dependence on the gold nanoparticle concentration suggests that aggregated nanospheres are responsible for the observed enhanced photothermal destruction of the cells.
Huang
Xiaohua
X
Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Qian
Wei
W
El-Sayed
Ivan H
IH
El-Sayed
Mostafa A
MA
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003287:Contrast Media; D066246:ErbB Receptors / Q000096:biosynthesis; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049329:Nanostructures / Q000737:chemistry*; D012542:Scattering, Radiation; D019265:Spectroscopy, Near-Infrared; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D006046:Gold; D066246:ErbB Receptors