Molecular and nanoparticulate agents for photodynamic therapy guided by near infrared imaging

Photodynamic therapy (PDT) of cancer is a clinically approved, minimally invasive therapeutic approach, combining PDT drug (photosensitizer, PS), molecular oxygen and light to induce cytotoxicity via reactive oxygen species (ROS), which are generated by the light excited PS. Most of the PS molecules fluoresce under excitation with light and fluorescence imaging (FLI) can be employed to evaluate their biodistribution and assess the intratumoral delivery before the therapeutic light application. Light absorption can also be utilized to track a PS by photoacoustic imaging (PAI). However, an excitation of the PS during assessment of its biodistribution through FLI or PAI results in premature photobleaching and causes toxicity. An involvement of a separate fluorescent (luminescent) or photoacoustic imaging probe, which provides imaging contrast in combination with PS without excitation of the latter, can allow for “see-and-treat” approach with FLI/PAI guided PDT. On the other hand, it is well-known that near-infrared (NIR) light is able to penetrate relatively deeper in comparison with visible light, due to reduced absorption and scattering. In addition to the conventional NIR window (NIR-I, ∼700–950 nm), other transparency windows for biological tissues have recently been identified at ∼1000–1700 nm (NIR-II), benefiting optical bioimaging due to the reduced tissue scattering and autofluorescence. Multiple NIR-II imaging probes are currently introduced both for luminescence and photoacoustic bioimaging, providing the significantly improved signal to noise ratio (SNR), imaging depth and resolution. Their combinations with PS are also being increasingly reported, though no review on this hot topic currently exists. Herein, a state-of-the-art in NIR photoluminescence (including fluorescence) and photoacoustic imaging guided PDT is presented. NIR-I and NIR-II spectral ranges are considered, along with both molecular and nanoparticle formulations for imaging guided PDT. It is expected that this review will provide a solid foundation for future translational studies in the domain of NIR imaging guided photodynamic therapy and drug delivery.