Table 2.
Overview of the advantages and disadvantages for the current opportunities of PDT.
| Challenge | Strategy to Overcome | Advantages | Disadvantages |
|---|---|---|---|
| Sensitizer biodistribution | Nanoparticle encapsulation | Control over pharmacokinetics, possibility of adding targeting moieties. | The enhanced-permeability and retention effect is much less pronounced in humans. |
| Antibody conjugation | Specific targeting of tumor epitopes, adoption of antibody biodistribution. | Lack of truly specific tumor targets. | |
| Peptide association | Targeting of tumor present ligands, adoption of peptide association. | Lack of truly specific ligands in the tumor. | |
| EV incorporation | Enhanced biodistribution of the PS, enhanced antitumor efficacy depending on the EV origin. | Large scale production is challenging. Restricted to the use of cell lines. | |
| Immune cells | Tunable distribution based on cell type and immunological state. Possibility to simultaneously use immune cells for therapy. | Restricted to distribution and functionality of immune cells in use. Distribution of PS to tumor cells required following death of carrier cells. | |
| Light propagation | NIR absorbing sensitizers | Increased penetration depth of light used for PDT. | High fluence required due to a reduced energy of therapeutic NIR light. |
| Upconversion Nanoparticles | Increased penetration depth of light used for PDT. Possibility to co-encapsulate additional therapeutic agents. | High fluence required due to a reduced energy of therapeutic NIR light. | |
| Hypoxia | O2-generating strategies | Possibility to increase ROS quantum yields after PDT. | Requires the use of carrier systems for O2-generating agents. |
| Hypoxia-responsive prodrugs | Drug selectivity to hypoxic areas in the body, such as the tumor. | Restricted to certain prodrugs that are hypoxia-responsive. | |
| O2 tumor diffusion | Increased availability of O2 for PDT throughout the tumor. | Requires PS or PDT protocols that can be directed to the ECM. | |
| Vascular disruption | Tumor vasculature disrupting agents | Enhanced tumor vasculature disruption. | Risk of adverse events of vasculature-disrupting agents. |
| Tumor vasculature targeting | Enhanced tumor vasculature disruption. | Risk of adverse events due to vasculature-destruction. | |
| VTP to enhance combination treatments | Increased potential for synergy with additional agent due to vasculature disruption. | Efficacy depending on ability of VTP to sufficiently disrupt the vasculature. | |
| Partial tumor destruction | Combination with chemotherapy | Increased antitumor efficacy. | Associated with a higher risk of adverse events. |
| Combination with other neoplastic agents | Increased antitumor efficacy. | Depending on the agent used, but often associated with increased risk of adverse events. | |
| Insufficient PDT-induced immune response | PDT-generated or enhanced tumor vaccines | Possibility to generate in situ vaccinations, or to enhance vaccination efficacy. Possibility to affect metastatic tumors. | Efficacy of the treatment is dependent on the ability of PDT to induce a pro-inflammatory environment in the tumor. |
| Combination with immunostimulatory agents | Increased antitumor efficacy, possibility to generate an in situ vaccination. Possibility to affect metastatic tumors. | Certain immunostimulatory compounds require encapsulation to prevent adverse events. | |
| Combination with immune checkpoint inhibition | Increased antitumor efficacy. Possibility to affect metastatic tumors. | Increased risk of adverse events |