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Photochem Photobiol. 2020 Jan 2. doi: 10.1111/php.13209. [Epub ahead of print]

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment.

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Fischell Department of Bioengineering, University of Maryland, College Park, MD.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, North Carolina State University, Raleigh, NC.
Department of Electrical and Computer Engineering, University of Maryland, College Park, MD.
Department of Physics, College of Science and Mathematics, University of Massachusetts at Boston, Boston, MA.
Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC.
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC.
Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD.


Targeting the tumor microenvironment (TME) provides opportunities to modulate tumor physiology, enhance the delivery of therapeutic agents, impact immune response and overcome resistance. Photodynamic therapy (PDT) is a photochemistry-based, nonthermal modality that produces reactive molecular species at the site of light activation and is in the clinic for nononcologic and oncologic applications. The unique mechanisms and exquisite spatiotemporal control inherent to PDT enable selective modulation or destruction of the TME and cancer cells. Mechanical stress plays an important role in tumor growth and survival, with increasing implications for therapy design and drug delivery, but remains understudied in the context of PDT and PDT-based combinations. This review describes pharmacoengineering and bioengineering approaches in PDT to target cellular and noncellular components of the TME, as well as molecular targets on tumor and tumor-associated cells. Particular emphasis is placed on the role of mechanical stress in the context of targeted PDT regimens, and combinations, for primary and metastatic tumors.


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