Fluorescence resonance energy transfer-based drug delivery systems for enhanced photodynamic therapy

Photodynamic therapy (PDT) has received increasing attention in disease treatment due to its minimally-invasive, selective destruction with a combination of a photosensitizer (PS), light, and oxygen. However, the limited cytotoxic singlet oxygen (1O2) generation and thin tissue penetrability have been two major barriers in conventional PDT, hindering its further development and clinical use. Recently, fluorescence resonance energy transfer-based drug delivery systems (FRET-DDSs), indirectly activating PS drugs by a donor fluorophore, have been successfully applied to alleviate these issues. The transfer of excitation energy from donors to PS drugs can significantly boost its light harvesting and extend the field of the light source, which dramatically improves its production efficiency of 1O2, thus leading to highly efficient and deep-tissue-penetrable PDT for the treatment of bacteria, cancer and other diseases. In this Review, we give the first-known overview of recent advances in FRET-DDSs for enhanced PDT. In particular, dependent on the excitation energy mechanism in the FRET process, six major types of FRET-DDSs, including one-photon, two-photon, upconversion, auto-fluorescence, X-ray, and Cerenkov excited FRET-DDSs, in PDT applications are summarized in detail. Furthermore, future research directions and perspectives in this emerging field are also discussed.