Development of "Smart" photodynamic theranostics agents

Photodynamic therapy (PDT) has been widely studied in recent decades owing to its effectiveness in killing cancer cells. By utilizing a photosensitizer and irradiating it with light of a specific wavelength, the photosensitizer can be activated to generate reactive oxygen species (ROS) through energy transfer processes in the presence of molecular oxygen. The ROS are responsible for causing damage, inhibiting cancer cell growth and even killing the cancer cells. Understandably, just like other cancer treatments, PDT is an intriguing idea that requires consistent refining to improve on the constraints such as photostability, selectivity and tissue penetration. It is a powerful means of treatment as the oxidizing power of ROS and strong and non-discriminative and the PDT process is minimally invasive. However, it is crucial to ensure (1) the ROS is generated at the desired regions of interests to avoid undesired damage to healthy cells and (2) the photosensitizer is sufficiently stable in its journey to reach the regions of interest.

The choice of excitation light has varied over the years of PDT research, with researchers trying to balance the penetration strength with the absorption ability of the photosensitizer. The development of multiphoton excitation is welcoming as near-infrared excitation is able to evade the absorption of biological tissues—known as the biological window; nevertheless, it is not an easy task to structurally design photosensitizers that could be excited by multiphoton excitation. Latest research explores the possibility of using X-ray as the excitation source to activate photosensitizers for generating ROS. X-ray has high tissue penetration ability and a low dosage of X-ray can ensure minimal radiation risks while maintaining effective excitation in vivo. The penetration depth and duration of photosensitizer excitation determines the efficacy of PDT treatments.

On the other hand, PDT agents, just like other modalities, requires target-specificity to minimize side effects and increase the overall treatment efficacy, thereby reducing the dosage amount. The stability of the photosensitizers is also vital to ensure the photosensitizers remain able to carry out its function to generate ROS at the designated target regions. Researchers have devoted an extraordinary amount of effort in modifying the structure to improve stability and most recently, the idea of using molecular nanoplatforms such as nano-micelles has been able to hit “two birds with one stone.” The nanoplatform benefits from the enhanced permeability and retention effect for tumor cell localization and the micellar structure protects photosensitizers from potential destruction and decomposition by encapsulation.

Encouraging results from recent PDT research showed us that there is still much unexplored potential in the development of PDT photosensitizers and we expect PDT to remain one of the most effective clinical means for cancer treatment in the near future. This review covers the recent development of PDT agents from simple molecular level to nanoparticles. Discussion on different classical frameworks and clinically approved photosensitizers are included as well. The potential development of photosensitizers is discussed for the advancement of PDT in the near future.