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Ultra‐Low Energy Threshold for Cancer Photothermal Therapy Using Transferrin‐Conjugated Gold Nanorods

Gold nanoparticles have shown potential applications for cancer detection and localized photothermal therapy (PTT). Among the gold nanoparticles that have been studied, gold nanorods are of particular interest because of their tuneable near-infrared (NIR) absorption and the recent success in their size-controlled, large-scale synthesis. The strong two-photon photoluminescence (TPL) of gold nanorods render them good contrast agents for cancer cell imaging under two-photon excitation, which makes it more suitable to three-dimensional nonlinear optical imaging of biological samples. Despite the successful application of gold nanorods in PTT and in vitro cancer imaging, this technique still has a long way to go before it can be implemented clinically. For clinical applications, the energy input should be as low as possible to avoid damage to healthy tissues, which is always a concern for laser-based applications. The energy threshold can be reduced by optimizing tumor targeting of the particles, choosing a suitable laser mode, and improving the light absorption efficiency of the nanorods. It has been observed that a pulsed femtosecond laser beam in PTT was more effective than a continuous wave (CW) laser beam. However, most of the gold nanorods are randomly oriented in cells, making it impossible to achieve the maximum energy efficiency due to the limited fraction of excitation of the total nanorods under linearly polarized light. To increase the light absorption efficiency and hence the photothermal effect of the nanorods, a circularly polarized laser beam, which can emit a light beam of all polarization angles within one optical period, can be used to activate as many nanorods as possible, as illustrated by Figure 1a. To demonstrate the circular polarization effect on nanorod excitation, nanorods from a dilute solution were deposited on a cover slide and the same population of nanorods was subject to a linearly and circularly polarized light illumination in sequence. The corresponding images of the nanorods are given in Figure 1b and 1c, respectively. Both single gold nanorods and aggregated nanorods (larger and brighter spots as circled in Fig. 1b) can be identified. It shows that under illumination of circularly polarized light at