Resonance Energy Transfer-Driven Photothermal Nanoagent Enables Melanoma Ablation Under Low-Power Near-Infrared...

Photothermal therapy (PTT) utilizes near-infrared (NIR) light to activate photothermal agents, enabling localized tumor ablation. However, conventional agents require high laser power densities to reach therapeutic temperatures, exceeding the skin safety limit of 0.33 W/cm², thereby limiting their clinical translation. Presented herein is a nanoplatform that utilizes resonance energy transfer (RET) to boost photothermal performance under clinically acceptable irradiation. The nanoagent, PC-Fe/Co-AuNRs@SiNc, integrates gold nanorods (AuNRs) coated with an ~3.5 nm bimetallic iron (Fe)-cobalt (Co) shell and the NIR dye silicon naphthalocyanine (SiNc), co-encapsulated within a polymeric carrier (PC). The Fe/Co shell functions as both a nanoscale spacer and a plasmonic modulator, red-shifting and amplifying the AuNR resonance, to enhance spectral overlap with SiNc and facilitate non-radiative energy transfer. Meanwhile, the polymer matrix ensures effective dye-plasmon coupling. Under low-power irradiation (0.25 W/cm², 780 nm), PC-Fe/Co-AuNRs@SiNc exhibits photothermal conversion efficiencies 6.6- and 3.3-fold higher than SiNc and Fe/Co-AuNRs alone, respectively, and 2.3-fold higher than an agent containing SiNc and AuNRs without the Fe/Co shell. In an aggressive transgenic melanoma model, a single treatment with systemically delivered PC-Fe/Co-AuNRs@SiNc, under the same low-power parameters, achieves complete tumor ablation. This work establishes RET as a transformative strategy for designing next-generation PTT agents.