Hypoxia-responsive near infrared thioxanthene-hemicyanine nanoparticle for multimodal imaging-guided photothermal/photodynamic therapy

Multimodal imaging-guided phototherapy is an emerging treatment for tumor elimination that can provide more physiological and pathological information for precise theranostics with minimal side effects. Herein, we proposed a novel hypoxia-activated near infrared (NIR) probe (AzoCyS-N) based on a thioxanthene-hemicyanine scaffold for tumor multimodal imaging and photothermal/photodynamic therapy. The thioxanthenehemicyanine fluorophore (CyS-NH2) could be released from AzoCyS-N via reductive cleavage of the azo group under hypoxia, resulting in a dramatically enhanced NIR fluorescence signal at 760 nm and redshifted absorption at 730 nm. AzoCyS-N was further encapsulated into a folic acid modified amphiphilic polymer to form AzoCyS-N NPs to further improve the tumor selectivity. In addition, the released Cys-NH2 could generate singlet oxygen and exhibited decent photothermal effects under 690 nm light irradiation. The in vivo studies confirmed that the NIR fluorescence and PA signals in the tumor region were selectively lightened after intravenous injection of AzoCySN NPs. Finally, solid tumor growth was significantly suppressed by the synergistic effect of PDT and PTT. This work provides a powerful multimode imaging-guided synergistic phototherapeutic system for precise tumor theranostics.

Automated summary

Multimodal imaging-guided phototherapy using a hypoxia-activated near infrared probe has been developed for tumor elimination. The probe can release a fluorescence group under hypoxia, leading to enhanced NIR fluorescence signal. Additionally, the released group can generate singlet oxygen and exhibit photothermal effects. In vivo studies demonstrated selective enhancement of fluorescence and photoacoustic signals in the tumor region. Furthermore, the synergistic effect of photodynamic therapy and photothermal therapy significantly suppressed tumor growth.