Clinically Translatable, Thermometrically Self-Regulating Photoacoustic Nanoaggregates for Precision-Guided Photothermal Therapy

Accurate temperature feedback is crucial for effective photothermal therapy (PTT). Here, a clinically translatable thermometrically self-regulating nanoaggregate (NA), JICG@PVP, composed of indocyanine green (ICG) J-type aggregates and polyvinylpyrrolidone, is proposed for precision-guided PTT with three-dimensional thermographic monitoring. These self-regulating NAs exhibit thermosensitive behavior in the 37–52 °C range, which can dissociate to clinically applicable ICG monomer molecules with ratiometric optical absorption changes at 780 and 895 nm, enabling precise temperature monitoring through a linear correlation between this absorption ratio and in situ temperature. Photoacoustic (PA) imaging demonstrates the NAs' ability to monitor temperature distributions at depths of up to 1.39 cm in tissue phantoms and 0.49 cm in pork tissues, with an accuracy of ±0.7 °C. In vivo studies confirmed the efficacy of these NAs in regulating temperature, with enhanced precision-guided therapeutic outcomes by achieving a tumor suppression rate of 93% with minimized thermal damage to normal tissues. Meanwhile, the real-time tracking through fluorescence imaging revealed that the prepared NAs were cleared through renal excretion after postinjection, demonstrating an excellent safety profile for clinical translation. The proposed self-regulating NAs featuring enhanced safety and superior therapeutic efficiency, provide a potential groundwork for clinical translation of PA thermographically guided PTT.