Antiquenching Macromolecular NIR‐II Probes with High‐Contrast Brightness for Imaging‐Guided Photothermal Therapy under 1064 nm Irradiation

Abstract Most NIR‐II fluorescent dyes, especially polymethine cyanine, face the inevitable self‐quenching phenomenon in an aqueous solution. This unacceptable property has severely limited their application in high‐resolution biological imaging. Here, a NIR‐II macromolecular probe (MPAE) is synthesized through the structure modification of molecule probe and the covalent coupling of an amphiphilic polypeptide, which presents considerable biocompatibility and negligible systemic side effect. The molecule probe's stereo structure and the polymer's conjugation could effectively prevent the π ‐ π stacking, thereby exhibiting excellent quenching resistance in aqueous solutions (absolute QY = 0.178%). This remarkable feature endows it with deeper tissue penetration than the clinically used indocyanine green (ICG) and high contrast brightness at the tumor site for the NIR‐II fluorescence imaging. Based on the effective accumulation of tumor sites and considerable photothermal conversion efficiency (40.07%), the MPAE‐NPS presents superior antitumor efficiency on breast tumor‐bearing mice under the 1064 nm irradiation without rebound or recurrence. All these outstanding performances reveal the great promise of MPAE‐NPS in Nano‐drug delivery and imaging‐assisted photothermal therapy in the NIR‐II window.