RESUMO
Photodynamic therapy is an anti-cancer treatment that requires illumination of photosensitizers to induce local cell death. Current near-infrared organic photosensitizers are built from large and non-modular structures that cannot be tuned to improve safety and minimize off-target toxicity. This work describes a novel chemical platform to generate enzyme-activatable near-infrared photosensitizers. We optimized the Se-bridged hemicyanine scaffold to include caging groups and biocompatible moieties, and generated cathepsin-triggered photosensitizers for effective ablation of human glioblastoma cells. Furthermore, we demonstrated that enzyme-activatable Se-bridged hemicyanines are effective photosensitizers for the safe ablation of microtumors in vivo, creating new avenues in the chemical design of targeted anti-cancer photodynamic therapy agents.
Assuntos
Raios Infravermelhos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Animais , Carbocianinas/química , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , CamundongosRESUMO
Optical imaging has become an indispensable technology in the clinic. The molecular design of cell-targeted and highly sensitive materials, the validation of specific disease biomarkers, and the rapid growth of clinically compatible instrumentation have altogether revolutionized the way we use optical imaging in clinical settings. One prime example is the application of cancer-targeted molecular imaging agents in both trials and routine clinical use to define the margins of tumors and to detect lesions that are "invisible" to the surgeons, leading to improved resection of malignant tissues without compromising viable structures. In this Perspective, we summarize some of the key research advances in chemistry, biology, and engineering that have accelerated the translation of optical imaging technologies for use in human patients. Finally, our paper comments on several research areas where further work will likely render the next generation of technologies for translational optical imaging.