Kexin Shi, Xinwei Wang, Yuxing Wang, Xia Long, Changli Shao, Jin Li
ABSTRACT Since the discovery of unique molecular building blocks (MBBs) such as tetraphenylethylene, aggregation‐induced emission fluorescence imaging probes have witnessed revolutionary progress. For plasmon‐free Raman imaging probes, the fundamental bottleneck is the discovery of unique Raman‐active MBBs to improve the intrinsic scattering. We herein proposed a new concept of quencher‐enhanced Raman scattering (QERS) based on nonfluorescent diammonium MBBs to fabricate bright Raman probes in second near‐infrared window through improving rigid electronic resonance scattering while simultaneously suppressing concomitant fluorescence backgrounds. The home‐made large π ‐conjugated diammonium quencher displays high photon‐absorption but ultra‐low fluorescence quantum yield (0.0001) under rigid resonant excitation at 1064 nm. Upon nanoprecipitation, these MBBs produce QERS probes with giant Raman cross‐section (1.27 × 10 −19 cm 2 ) as well as remarkable photostability, enabling high‐precision Raman‐guided surgical removal of tumor in living mice. Moreover, QERS probes achieve a high photothermal conversion efficiency up to 60.5%, allowing for effective hyperthermia ablation of drug‐resistant bacteria in postsurgical infected wounds in the mice. QERS may suggest a robust and efficient strategy for developing plasmon‐free Raman probes.