Issue 17, 2020

H2S-Donating trisulfide linkers confer unexpected biological behaviour to poly(ethylene glycol)–cholesteryl conjugates

Abstract

Inspired by the properties of the naturally occurring H2S donor, diallyl trisulfide (DATS, extracted from garlic), the biological behaviour of trisulfide-bearing PEG-conjugates was explored. Specifically, three conjugates comprising an mPEG tail and a cholesteryl head were investigated: conjugates bridged by a trisulfide linker (T), a disulfide linker (D) or a carbamate linker (C), and a fourth comprising two mPEG tails bridged by a trisulfide linker (P). H2S testing using both a fluorescent chemical probe in HEK293 cells and an amperometric sensor to monitor release in suspended cells, demonstrated the ability of the trisulfide conjugates, T and P, to release H2S in the presence of cellular thiols. Cytotoxicity and cyto-protective capacity on HEK293 cells showed that T was the best tolerated of the conjugates studied, and remarkably more so than D or C. Moreover, it was noted that application of T conferred a protective effect to the cells, effectively abolishing the toxicity associated with co-administered C. The interaction of conjugates and combinations thereof with the cell membrane of HEK cells, as well as ROS generation were also investigated. It was found that C caused significant membrane perturbation, correlating with high losses in cell viability and pronounced generation of ROS, especially in the mitochondria. T, however, did not disturb the membrane and was able to mitigate the generation of ROS, especially in the mitochondria. The interplay of the cholesteryl group and H2S donation for conferring cytoprotective effects was clearly demonstrated as P did not display the same beneficial characteristics as T.

Graphical abstract: H2S-Donating trisulfide linkers confer unexpected biological behaviour to poly(ethylene glycol)–cholesteryl conjugates

Supplementary files

Article information

Article type
Paper
Submitted
20 ное 2019
Accepted
19 мар 2020
First published
30 мар 2020

J. Mater. Chem. B, 2020,8, 3896-3907

H2S-Donating trisulfide linkers confer unexpected biological behaviour to poly(ethylene glycol)–cholesteryl conjugates

F. Ercole, Y. Li, M. R. Whittaker, T. P. Davis and J. F. Quinn, J. Mater. Chem. B, 2020, 8, 3896 DOI: 10.1039/C9TB02614B

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.

Social activity

Spotlight

Advertisements