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Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain
Author(s) -
Inglut Collin T.,
Gaitan Brandon,
Najafali Daniel,
Lopez Irati Abad,
Connolly Nina P.,
Orsila Seppo,
Perttilä Robert,
Woodworth Graeme F.,
Chen Yu,
Huang HuangChiao
Publication year - 2019
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13155
Subject(s) - photodynamic therapy , protoporphyrin ix , singlet oxygen , photobleaching , brain tumor , glioma , brain tissue , light energy , fluorescence , medicine , biomedical engineering , pathology , nuclear medicine , chemistry , cancer research , optics , oxygen , physics , organic chemistry
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.