Dual-laser “808 and 1,064 nm” strategy that circumvents the Achilles’ heel of photothermal therapy

Breast cancer has now overtaken lung cancer as the "world's leading cancer," yet detecting and implementing effective therapies remains a significant challenge. Substantial advances have been made in photothermal therapy (PTT), where photosensitizers use photonic energy to induce localized hyperthermia for cancer eradication. This pioneering approach is gaining traction in clinical settings. However, traditional PTT faces inherent limitations, including the risk of damage to neighboring healthy tissues and potential inflammatory responses due to overheating. Drawing inspiration from the distinct characteristics of aggregation-induced emission the small molecule, PM331, was chosen for study. This donor-acceptor-donor system displays good photothermal conversion efficiencies (40% and 66%) upon excitation at 808 nm and 1,064 nm, respectively. It is also characterized by attractive optical features in the second near-infrared (NIR-II) window. Using nanoparticles containing PM331, <b>PM331@F127</b>, we have developed a PTT strategy, termed dual-laser PTT (DLPTT), that involves successive excitation using 808 nm and 1,064 nm lasers guided by both NIR-II fluorescence and photoacoustic imaging. The DLPTT strategy involves two steps. First, it initiates DNA damage and downregulates heat shock protein expression as the result of an initial brief irradiation with an 808 nm laser. This is then followed by irradiation with a 1,064 nm laser to ablate tumor cells while minimizing inflammation and harm to surrounding healthy tissues. Based on the findings reported here, we suggest that DLPTT could represent an attractive approach to precision medicine and one that could make PTT more amenable to clinical implementation.