An EPR strategy for bio-responsive fluorescence guided surgery with simulation of the benefit for imaging.
journal contributionposted on 2021-01-18, 17:16 authored by Harrison C Daly, Emer Conroy, Mihai Todor, Dan WuDan Wu, William M Gallagher, Donal O'SheaDonal O'Shea
A successful matching of a PEG group size with the EPR effect for an off-to-on responsive NIR-fluorophore conjugate has been accomplished which allows two distinct in vivo tumor imaging periods, the first being the switch on during the initial tumor uptake via enhanced permeability into the ROI (as background is suppressed) and a second, later, due to enhanced retention within the tumor.
Methods: Software simulation (https://mihaitodor.github.io/particle_simulation/index.html), synthetic chemistry, with in vitro and in vivo imaging have been synergistically employed to identify an optimal PEG conjugate of a bio-responsive NIR-AZA fluorophore for in vivo tumor imaging.
Results: A bio-responsive NIR-AZA fluorophore conjugated to a 10 kDa PEG group has shown excellent in vivo imaging performance with sustained high tumor to background ratios and peak tumor emission within 24 h. Analysis of fluorescence profiles over 7 days has provided evidence for the EPR effect playing a positive role.
Conclusion: Preclinical results show that exploiting the EPR effect by utilizing an optimized PEG substituent on a bio-responsive fluorophore may offer a means for intraoperative tumor margin delineation. The off-to-on responsive nature of the fluorophore makes tumor imaging achievable without waiting for clearance from normal tissue.
Project Ireland 2040 Disruptive Technology Innovation Fund and Science Foundation Ireland grant number 11/PI/1071(T).
Irish Cancer Society Collaborative Cancer Research Centre Breast-Predict (CCRC13GAL).
Associated research data filesSupplementary material available at: https://www.thno.org/v10p3064.htm#SM0
CommentsThe original article is available at https://www.thno.org/ Pre-print is available on ChemRxiv https://doi.org/10.26434/chemrxiv.11316227.v1 and RCSI repository https://hdl.handle.net/10779/rcsi.16997980.v1
Published CitationDaly HC, Conroy E, Todor M, Wu D, Gallagher WM, O'Shea DF. An EPR strategy for bio-responsive fluorescence guided surgery with simulation of the benefit for imaging. Theranostics. 2020;10(7):3064-3082.
Publication Date10 Feb 2020
- Surgical Science and Practice
- Chemistry and Pharmaceutical Sciences
PublisherIvyspring International Publisher
- Published Version (Version of Record)