Resonance Energy Transfer–Driven Photothermal Nanoagent Enables Melanoma Ablation Under Low‐Power Near‐Infrared Irradiation

ABSTRACT 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/cm 2 , 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/cm 2 , 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.