Low Power Single Laser Activated Synergistic Cancer Phototherapy Using Photosensitizer Functionalized Dual Plasmonic Photothermal Nanoagents.

Combination therapy, especially photodynamic/photothermal therapy (PDT/PTT), has shown promising applications in cancer therapy. However, sequential irradiation by two different laser sources and even the utilization of single high-power laser to induce either combined PDT/PTT or individual PTT will be subjected to prolonged treatment time, complicated treatment process, and potential skin burns. Thus, low power single laser activatable combined PDT/PTT is still a formidable challenge. Herein, we propose an effective strategy to achieve synergistic cancer phototherapy under low power single laser irradiation for short duration. By taking advantage of dual plasmonic PTT nanoagents (AuNRs/MoS2), a significant increase in temperature up to 60 °C with an overall photothermal conversion efficiency (PCE) of 68.8% was achieved within 5 min under very low power (0.2 W/cm2) NIR laser irradiation. The enhanced PCE and PTT performance is attributed to the synergistic plasmonic PTT effect (PPTT) of dual plasmonic nanoagents, promoting simultaneous release (85%) of electrostatically bonded indocyanine green (ICG) to induce PDT effects, offering simultaneous PDT/synergistic PPTT. Both in vitro and in vivo investigations reveal complete cell/tumor eradication, implying that simultaneous PDT/synergistic PPTT effects induced by AuNRs/MoS2-ICG are much superior over individual PDT or synergistic PPTT. Notably, synergistic PPTT induced by dual plasmonic nanoagents also demonstrates higher in vivo antitumor efficacy than either individual PDT or PTT agents. Taken together, under single laser activation with low power density, the proposed strategy of simultaneous PDT/synergistic PPTT effectively reduces the treatment time, achieves high therapeutic index, and offers safe treatment option, which may serve as a platform to develop safer and clinically translatable approaches for accelerating cancer therapeutics.