Chemiluminescence-Guided Cancer Therapy Using a Chemiexcited Photosensitizer

Image-guided therapy is one of the most promising strategies for efficiently curing a tumor. Here, a novel nanomaterial with chemiexcited far-red/near-infrared (FR/NIR) emission and singlet oxygen (¹O₂) generation is reported for precise diagnosis and treatment of tumors. Bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO) and a specially designed photosensitizer TBD with aggregation-induced FR/NIR emission were co-encapsulated by pluronic F-127 and soybean oil to form C-TBD nanoparticles (C-TBD NPs). These NPs serve as a specific H₂O₂ probe to precisely track tumors in vivo through chemiluminescence imaging. In addition, effective ¹O₂ generation by C-TBD NPs in response to tumor H₂O₂ was observed, which could efficiently induce tumor cell apoptosis and inhibit tumor growth. Both the chemiluminescence response and the therapeutic function were further enhanced when β-phenylethyl isothiocyanate was used to enhance the H₂O₂ production at the tumor site. Our results prove that C-TBD NPs provide a new strategy for intelligent, accurate, and non-invasive tumor therapy. Precise image-guided therapy is key to eradicating tumors in clinical practice. Here, we report a new nanomaterial based on a chemiexcited photosensitizer, which can be specifically activated by H₂O₂ within the tumor environment to produce far-red/near-infrared luminescence and singlet oxygen. Using such a nanoparticle, primary and metastatic breast tumors can be clearly identified through chemiluminescence imaging with a very high signal-to-noise ratio. Accompanied by the use of an anti-tumor drug, FEITC, the signal of the tumor could be further enhanced as a result of elevated H₂O₂ production at the tumor site. More importantly, specific tumor killing can be achieved through chemiexcited singlet oxygen production, and the effect of therapy is also increased in the presence of FEITC. Considering the multiple advantages of simultaneous tumor theranostics, our nanoparticle design represents a promising strategy for future clinical tumor therapy. Organic nanoparticles exhibiting intense FR/NIR chemiluminescence and strong chemiexcited singlet oxygen generation in the presence of H₂O₂ have been successfully used for selective tumor imaging and therapy. Both tumor chemiluminescent signals and singlet oxygen production can be further enhanced in the presence of an anti-tumor drug, FEITC, which could increase the amount of H₂O₂ at the tumor site for effective tumor treatment. Our design represents a new strategy for light-source-free image-guided tumor therapy.