Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain.

Autor: Inglut CT; Fischell Department of Bioengineering, University of Maryland, College Park, MD., Gaitan B; Fischell Department of Bioengineering, University of Maryland, College Park, MD., Najafali D; Fischell Department of Bioengineering, University of Maryland, College Park, MD., Lopez IA; Fischell Department of Bioengineering, University of Maryland, College Park, MD., Connolly NP; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD.; Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD., Orsila S; Modulight, Inc., Tampere, Finland., Perttilä R; Modulight, Inc., Tampere, Finland., Woodworth GF; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD.; Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD., Chen Y; Fischell Department of Bioengineering, University of Maryland, College Park, MD.; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD., Huang HC; Fischell Department of Bioengineering, University of Maryland, College Park, MD.; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD.
Jazyk: angličtina
Zdroj: Photochemistry and photobiology [Photochem Photobiol] 2020 Mar; Vol. 96 (2), pp. 301-309. Date of Electronic Publication: 2019 Oct 13.
DOI: 10.1111/php.13155
Abstrakt: Fluorescence-guided surgery (FGS) is routinely utilized in clinical centers around the world, whereas the combination of FGS and photodynamic therapy (PDT) has yet to reach clinical implementation and remains an active area of translational investigations. Two significant challenges to the clinical translation of PDT for brain cancer are as follows: (1) Limited light penetration depth in brain tissues and (2) Poor selectivity and delivery of the appropriate photosensitizers. To address these shortcomings, we developed nanoliposomal protoporphyrin IX (Nal-PpIX) and nanoliposomal benzoporphyrin derivative (Nal-BPD) and then evaluated their photodynamic effects as a function of depth in tissue and light fluence using rat brains. Although red light penetration depth (defined as the depth at which the incident optical energy drops to 1/e, ~37%) is typically a few millimeters in tissues, we demonstrated that the remaining optical energy could induce PDT effects up to 2 cm within brain tissues. Photobleaching and singlet oxygen yield studies between Nal-BPD and Nal-PpIX suggest that deep-tissue PDT (>1 cm) is more effective when using Nal-BPD. These findings indicate that Nal-BPD-PDT is more likely to generate cytotoxic effects deep within the brain and allow for the treatment of brain invading tumor cells centimeters away from the main, resectable tumor mass.
(© 2019 American Society for Photobiology.)
Databáze: MEDLINE
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