Scarpa, E;
Janeczek, AA;
Hailes, A;
de Andrés, MC;
De Grazia, A;
Oreffo, ROC;
Newman, TA;
(2018)
Polymersome nanoparticles for delivery of Wnt-activating small molecules.
Nanomedicine: Nanotechnology, Biology and Medicine
, 14
(4)
pp. 1267-1277.
10.1016/j.nano.2018.02.014.
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Abstract
Spatiotemporal control of drug delivery is important for a number of medical applications and may be achieved using polymersome nanoparticles (PMs). Wnt signalling is a molecular pathway activated in various physiological processes, including bone repair, that requires precise control of activation. Here, we hypothesise that PMs can be stably loaded with a small molecule Wnt agonist, 6-bromoindirubin-3′-oxime (BIO), and activate Wnt signalling promoting the osteogenic differentiation in human primary bone marrow stromal cells (BMSCs). We showed that BIO-PMs induced a 40% increase in Wnt signaling activation in reporter cell lines without cytotoxicity induced by free BIO. BMSCs incubated with BIO-PMs showed a significant up-regulation of the Wnt target gene AXIN2 (14 ± 4 fold increase, P < 0.001) and a prolonged activation of the osteogenic gene RUNX2. We conclude that BIO-PMs could represent an innovative approach for the controlled activation of Wnt signaling for promoting bone regeneration after fracture.
| Type: | Article |
|---|---|
| Title: | Polymersome nanoparticles for delivery of Wnt-activating small molecules |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nano.2018.02.014 |
| Publisher version: | https://doi.org/10.1016/j.nano.2018.02.014 |
| Language: | English |
| Additional information: | © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Polymersomes, Wnt, Drug delivery |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10075265 |
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