Abstract

Photodynamic therapy is commonly believed to target mitochondria when porphyrin and other photosensitizers are employed. We have used multiphoton metabolic imaging of cellular NAD(P)H as to monitor the effects of Photofrin, a porphyrin photosensitizer. Both Photofrin and NADH can simultaneously be multiphoton excited with 750 nm irradiation. In both monolayer cells and multicell tumor spheroids, Photofrin is seen to cause approximately two-fold reduction of NAD(P)H autofluorescence. From observations of autofluorescence during uptake, it appears that this decrease is concurrent with Photofrin entering the plasma membrane. During PDT, NAD(P)H is observed to decrease in a dose dependent manner for relatively short irradiations. Unexpectedly, this trend eventually reverses and the signal has been observed to increase as much as 5 fold from pre-PDT levels during therapy. We are currently assessing the significance of these observations and testing hypothetical mechanisms that might explain this behavior.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR004224-13
Application #
6349416
Study Section
Project Start
2000-09-01
Project End
2001-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
13
Fiscal Year
2000
Total Cost
$17,207
Indirect Cost

  Institution

Name
Cornell University
Department
Type
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Migone, Fernando F; Cowan, Robert G; Williams, Rebecca M et al. (2016) In vivo imaging reveals an essential role of vasoconstriction in rupture of the ovarian follicle at ovulation. Proc Natl Acad Sci U S A 113:2294-9
O'Dell, Ryan S; Cameron, David A; Zipfel, Warren R et al. (2015) Reelin Prevents Apical Neurite Retraction during Terminal Translocation and Dendrite Initiation. J Neurosci 35:10659-74
Byrnes, Laura J; Singh, Avtar; Szeto, Kylan et al. (2013) Structural basis for conformational switching and GTP loading of the large G protein atlastin. EMBO J 32:369-84
Jain, Manu; Robinson, Brian D; Scherr, Douglas S et al. (2012) Multiphoton microscopy in the evaluation of human bladder biopsies. Arch Pathol Lab Med 136:517-26
Degala, Satish; Williams, Rebecca; Zipfel, Warren et al. (2012) Calcium signaling in response to fluid flow by chondrocytes in 3D alginate culture. J Orthop Res 30:793-9
O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A et al. (2012) Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone. Neural Dev 7:25
McMullen, J D; Kwan, A C; Williams, R M et al. (2011) Enhancing collection efficiency in large field of view multiphoton microscopy. J Microsc 241:119-24
Kim, Sally A; Sanabria, Hugo; Digman, Michelle A et al. (2010) Quantifying translational mobility in neurons: comparison between current optical techniques. J Neurosci 30:16409-16
Bowles, Robby D; Williams, Rebecca M; Zipfel, Warren R et al. (2010) Self-assembly of aligned tissue-engineered annulus fibrosus and intervertebral disc composite via collagen gel contraction. Tissue Eng Part A 16:1339-48
McMullen, Jesse D; Zipfel, Warren R (2010) A multiphoton objective design with incorporated beam splitter for enhanced fluorescence collection. Opt Express 18:5390-8

Showing the most recent 10 out of 68 publications