Pyrrolopyrrole Cyanine-Based Polymer with Superior Multifunctionality for Boosting Cancer Phototheranostics

Molecular agents with exceptional multifunctionality are highly sought for phototheranostic applications. Herein we present a high-performance polymer for near-infrared II (NIR-II) fluorescence and photoacoustic (PA) imaging-guided mild photothermal therapy (mPTT) of tumors. We synthesize a series of semiconducting polymers based on pyrrolopyrrole cyanine, identifying that P(P-T) exhibits large mass extinction coefficient (139 L g –1 cm –1 ), excellent photothermal performance, bright NIR-II fluorescence, and PA imaging signals, making it among the highest-performing polymers in these properties. A tumor-targeting agent was developed by coencapsulating the high-performance polymer with a heat shock protein (HSP) inhibitor and camouflaging with M1 macrophage membranes. The integration of NIR-II fluorescence and PA imaging enables comprehensive tumor site delineation, guiding subsequent therapeutic intervention. In 4T1 tumor-bearing mice, the synergistic effect of mPTT under low-power 808 nm laser irradiation, combined with HSP inhibition, resulted in significant tumor suppression. This work offers valuable insights for designing advanced phototheranostic agents.