Raman Thermometry Nanopipettes in Cancer Photothermal Therapy

Raman thermometry based on surface-enhanced Raman scattering has been developed using nanopipettes in cancer cell photothermal therapy (PTT). Gold nanorods (AuNRs) are robustly epoxied on glass pipettes with a high surface coverage of ∼95% and less than 10 nm-wide nanogaps for intracellular thermometry and photothermal cancer therapy. The temperature changes could be estimated from the N≡C band shifts of 4-fluorophenyl isocyanide (FPNC)-adsorbed AuNRs on the Raman thermometry nanopipette (RTN) surfaces. An intracellular temperature change of ∼2.7 °C produced by altering the [Ca2+] in A431 cells was detected using the RTN in vitro, as checked from fura-2 acetoxymethyl ester (fura-2 AM) fluorescence images. For in vivo experiments, local temperature rises of ∼19.2 °C were observed in the mouse skin, whereas infrared camera images could not tract due to spatial resolution. In addition, a tumor growth suppression was observed in the PTT processes after an administration of the three AuNR-coated nanopipettes combined with a 671 nm laser irradiation for 5 min in 30 days. These results demonstrate not only the localized temperature sensing ability of FPNC-tagged AuNR nanopipettes in cell biology but also anti-cancer effects in photothermal cancer therapy.