Photodynamic therapy (PDT) is an approach to cancer therapy that uses a class of drugs that are called photosentisizers (PS) and light. When the PS is exposed to light of appropriate wavelength(s), it is able to produce reactive oxygen species (ROS) that interfere with many key processes of cell metabolism to cause cell necrosis or/and apoptosis, and eventually destruction of target tissues. Despite their effectiveness and promising future in cancer treatment, current PS lack tumor selectivity which limits their application in oncologic therapy due to serious side effects. Fluorogen activating proteins (FAPs) are a genetically encodable tag that can recognize and enhance fluorescence of otherwise dark molecules (fluorogens). Here we report a photosentisizing dye-FAP complex for selective targeting and destruction of cancer cells. Upon near infrared illumination, a FAP-bound di-iodo-malachite green fluorogen (MG2I) is able to specifically generate singlet oxygen and induce acute cytotoxity and cell death. We have achieved effective and specific cell killing with both genetically targeted FAP in different cellular compartments and FAP-affinity probes targeting for cancer cells. This method may greatly reduce the nonspecific toxicity to normal tissues due to the low phototoxicity from unbound dye and low off site singlet oxygen generation from untargeted complex. This method could have significant applications in tumor ablation, in basic research, and in regenerative medicine.

Activatable two-component photosentisizer: selective targeting and killing of cancer cells

249th National Meeting (2015)

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