Light-activated, photosensitizer-based therapies have been established as safe modalities of tumour ablation for numerous cancer indications. Two main approaches are available: photodynamic therapy, which results in localized chemical damage in the target lesions, and photothermal therapy, which results in localized thermal damage. Whereas the administration of photosensitizers is a key component of photodynamic therapy, exogenous photothermal contrast agents are not required for photothermal therapy but can enhance the efficiency and efficacy of treatment. Over the past decades, great strides have been made in the development of phototherapeutic drugs and devices as cancer treatments, but key challenges have restricted their widespread clinical use outside of certain dermatological indications. Improvements in the tumour specificity of photosensitizers, achieved through targeting or localized activation, could provide better outcomes with fewer adverse effects, as could combinations with chemotherapies or immunotherapies. In this Review, we provide an overview of the current clinical progress of phototherapies for cancer and discuss the emerging preclinical bioengineering approaches that have the potential to overcome challenges in this area and thus improve the efficiency and utility of such treatments.
Photodynamic therapy is predicated on the localized activation of photosensitizers within tumours in order to induce chemical damage and thus the death of tumour cells; this approach has been used in the clinic for >40 years for the treatment of diverse cancers, including superficial skin lesions and oesophageal and lung tumours.
Photothermal therapy (PTT) agents, which can be used to increase the efficiency of localized light-based heating and ablation of tumour tissues, have not yet been tested in large clinical trials; laser ablation without PTT agents has been used clinically.
Relative to single-modality approaches, drug–device combinations complicate clinical development; therefore, compelling efficacy and safety benefits are needed to support the use of such platforms in favour of competing ablative therapies.
Novel preclinical phototherapy agents have been engineered with advanced targeting and activation mechanisms.
These next-generation molecules and nanomaterials hold the potential to reduce adverse effects and/or improve the effectiveness of photodynamic therapy and PTT, leading to better outcomes and increased clinical adoption.
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The work of the authors is supported by the National Research Foundation of Korea (NRF), which is funded by the Korean government Ministry of Science (grant 2012R1A3A2048814 to J.Y.), the US NIH (grants R01EB017270 and DP5OD017898 to J.F.L.), the US National Science Foundation (grant 1555220 to J.F.L.), and the Intramural Research Program (IRP) of the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) (X.C.). The authors would like to thank Dr David Kessel for providing valuable feedback on the manuscript and Tian Guo and Rui Wang for their assistance in formatting the manuscript.
Nature Reviews Clinical Oncology thanks Liang Cheng, Michael R. Hamblin, Zhuang Liu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
J.F.L. holds stocks in POP Biotechnologies. The other authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Light-absorbing molecules that impart colour.
Chromophores that generate reactive oxygen species upon irradiation.
- Singlet state
A molecular quantum state in which all the electron spins are paired.
- Triplet state
A molecular quantum state in which an excited electron spin is unpaired.
- Fluence rate
The radiant energy incident per second crossing a sectional area of an irradiated spot, equating to the light power transferred per unit area, for example, in W/cm2 (1 W = 1 J/s).
- Total fluence
The total energy of light crossing a sectional area of an irradiated spot (exposed light energy per unit area, J/cm2).
Oligonucleotides or peptides that bind to a specific target molecule.
- Absorption maxima
The specific wavelength of light that chromophores absorb most intensely.
- Two-photon excitation
Simultaneous excitation by two photons at double the excitation wavelength.
- Upconverting nanoparticles
Particles that convert near-infrared excitation light into visible and ultraviolet emission light.
- Quenching moiety
A molecule that attenuates the fluorescence or singlet oxygen generation of a fluorophore or photosensitizer.
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Li, X., Lovell, J.F., Yoon, J. et al. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat Rev Clin Oncol 17, 657–674 (2020). https://doi.org/10.1038/s41571-020-0410-2
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