Issue 11, 2018

Cyclopeptidic photosensitizer prodrugs as proteolytically triggered drug delivery systems of pheophorbide A: part II – co-loading of pheophorbide A and black hole quencher

Abstract

Previously, we have shown that the use of a cyclopeptidic carrier could be of great interest for the design of fully characterized prodrugs for further use in photodynamic therapy. In order to further optimize the design, we decided to modify the highly quenched conjugate uPA-cPPP4/5 by co-loading a long-distance fluorescence quencher. For this purpose we tethered two black hole quenchers (BHQ3) together with two pheophorbide A moities onto the same PEGylated backbone and assessed the modified photophysical properties. In addition, to prove the reliability of our concept, we designed two analogues, uPA-cPPQ2+2/5 and CathB-cPPQ2+2/5, by using two different peptidic linkers as substrates for uPA and cathepsin B, respectively. These two conjugates proved to be much more water-soluble than their analogues bearing only Phas. These conjugates are not only highly quenched in their native state with regard to their fluorescence emission (up to 850 ± 287 times less fluorescent for CathB-cPPQ2+2/5 as compared to the unquenched monosubstituted reference uPA-cPPP1/5), but also prevent singlet oxygen production (with a total quenching of the emission when the quenchers are co-loaded with photosensitizers) when the photosentistizers are excited. After proteolytic activation, these conjugates recover their photophysical properties in the same way as occurred for uPA-cPPP4/5, with up to a 120-fold increase in fluorescence emission for uPA-cPPQ2+2/5 after two hours of incubation with uPA.

Graphical abstract: Cyclopeptidic photosensitizer prodrugs as proteolytically triggered drug delivery systems of pheophorbide A: part II – co-loading of pheophorbide A and black hole quencher

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
16 Հլս 2018
Accepted
28 Օգս 2018
First published
30 Օգս 2018

Photochem. Photobiol. Sci., 2018,17, 1739-1748

Cyclopeptidic photosensitizer prodrugs as proteolytically triggered drug delivery systems of pheophorbide A: part II – co-loading of pheophorbide A and black hole quencher

J. Bouilloux, O. Yuschenko, B. Dereka, G. Boso, A. Babič, H. Zbinden, E. Vauthey and N. Lange, Photochem. Photobiol. Sci., 2018, 17, 1739 DOI: 10.1039/C8PP00318A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements