Antiaggregation of NIR‐II Probe Regulated by Amphiphilic Polypeptide with High Contrast Brightness for Phototheranostics and Vascular Microscopic Imaging under 1064 nm Irradiation

Abstract Thanks to deep penetration and high resolution, the second near‐infrared window (NIR‐II, 1000–1700 nm) fluorescence (FL) imaging is expected to gain favor in clinical applications, including macroscopic imaging for cancer diagnosis and microangiography for vascular‐related disease diagnosis. Nevertheless, most NIR‐II fluorescent probes, especially cyanine, are highly susceptible to self‐quenching in the aggregated state, which severely limits their application in bioimaging. Here, the Br‐modified cyanine dye F 4 ‐Br and the amphiphilic polypeptide poly(oligo[ethylene glycol]methacrylate)‐ b ‐poly(benzyl‐L‐aspartic acid) (POEGMA‐PBLA) are synthesized. By modulating the self‐assembly of F 4 ‐Br and POEGMA‐PBLA to effectively inhibit the H‐aggregation of F 4 ‐Br in aqueous solutions, nanoprobe F 4 ‐Br@P 17 with outstanding antiquenching capability is developed. This prominent feature allows it to perform vascular microscopic imaging with high spatiotemporal resolution and assess hemodynamic characteristics. F 4 ‐Br@P 17 nanoparticles (NPs) with good stability and satisfactory biocompatibility also enable high contrast brightness for NIR‐II FL imaging of tumors. Given the efficient enrichment at tumor sites and the promising photothermal conversion efficiency (43.5%), F 4 ‐Br@P 17 NPs successfully conduct photothermal therapy and exhibit superior antitumor efficiency under 1064 nm laser irradiation. These remarkable performances reveal the tremendous possibility of F 4 ‐Br@P 17 NPs for in vivo microscopic imaging and FL imaging‐guided photothermal therapy in the NIR‐II region.