Molecular Regulation of Polymeric Raman Probes for Ultrasensitive Microtumor Diagnosis and Noninvasive Microvessle Imaging

Abstract Raman imaging is a powerful tool for the diagnosis of cancers and visualization of various biological processes. Polymers possessing excellent biocompatibility are promising probes for Raman imaging. However, few polymers are reported to serve as Raman probes for in vivo imaging, mainly due to the intrinsic weak Raman signal intensity and fluorescence interference of these polymers. Herein, a poly(indacenodithiophene‐benzothiadiazole) (IDT‐BT) polymer is presented, which emits unprecedentedly strong Raman signals under the near‐infrared wavelength (785 nm) excitation, thus functioning as a Raman probe for ultrasensitive in vivo Raman imaging. Further mechanistic studies unveil that the unique Raman feature of the IDT‐BT polymer relies on molecularly regulating its absorbance edge adjacent to the desired excitation wavelength, thus avoiding fluorescence interference and simultaneously emitting strong Raman scattering under preresonant excitation. Taking advantage of this discipline, the IDT‐BT polymeric probe successfully realizes intraoperative Raman imaging of micrometastasis as small as 0.3 mm × 0.3 mm, comparable to the most sensitive Raman probes currently reported. Impressively, the IDT‐BT enables noninvasive microvascular imaging, which is not achieved using other Raman probes. This work opens a new avenue toward the development of polymeric Raman probes for in vivo Raman imaging.