Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 4, Pages 1267-1277Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.02.014
Keywords
Polymersomes; Wnt; Drug delivery
Funding
- Medical Research Council, United Kingdom [MR/J004103/1]
- Wessex Medical Research, UoS Research Management Committee, Nanoear FP6 [FP-6 NMP4-CT-2006]
- Malaya University, Malaysia
- Institute for Life Sciences, Southampton, U.K.
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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. (C) 2018 The Authors. Published by Elsevier Inc.
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