作者：  Collin T. Inglut1,+, Brandon Gaitan1,+, Daniel Najafali1, Irati Abad Lopez1, Nina P. Connolly2,3, Seppo Orsila4, Robert Perttilä4, Graeme F. Woodworth2,3, Yu Chen1,2, Huang-Chiao Huang1,2*

 

1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA 

2Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA 

3Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA 

4Modulight, Inc., Hermiankatu 22, FI-33720, Tampere, Finland

 

摘要：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: 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.