Realizing a Record Photothermal Conversion Efficiency of Spiky Gold Nanoparticles in the Second Near-Infrared Window by Structure-Based Rational Design

The current technical dilemma for gold nanoparticles as photothermal (PT) transducers in cancer therapy is that strong absorption in the second near-infrared (NIR) window is accompanied by strong scattering of the NIR light, which then overrides the absorption, thus significantly weakening the light-to-heat conversion efficiency. Here we successfully prepared spiky gold nanoparticles (spiky Au NPs) with a controlled number of spikes, designed according to our simulations and experimentally verified. Their overall sizes and the numbers, lengths, and widths of the spikes were judiciously adjusted to locate their surface plasmon resonance peaks in the second NIR window and also to achieve a higher absorption-to-extinction ratio. As a result, the spiky Au NPs with optimal size and 6 spikes exhibited a record light-to-heat conversion efficiency (78.8%) under irradiation by 980 nm light. After surface PEGylation and conjugation with a lactoferrin (LF) ligand on the resulting spiky Au NPs, they in vivo displayed long circulation time (blood circulation half-life of ∼300 min) and high tumor accumulation due to their larger surface-to-volume ratio. Therefore, spiky Au NPs allowed complete ablation of tumors without recurrence merely after 3 min of light irradiation at 980 nm, opening up promising prospects of cancer photothermal therapy.