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Polymersome nanoparticles for delivery of Wnt-activating small molecules

Polymersome nanoparticles for delivery of Wnt-activating small molecules
Polymersome nanoparticles for delivery of Wnt-activating small molecules

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.

Drug delivery, Polymersomes, Wnt
1549-9634
1267-1277
Scarpa, Edoardo
e7d094b2-e64f-4b4c-a452-d478a912b171
Janeczek, Agnieszka A.
71e60ef8-107b-44bd-9c0c-18d5e534ff21
Hailes, Alethia
7b0cacd6-8fac-4898-a925-4818a35abea0
de Andrés, Maria C.
54e87e8a-1aa2-4907-a8a0-25d0c15e5e40
De Grazia, Antonio
ca329577-0e10-424e-a104-af068c935f07
Oreffo, Richard OC
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Scarpa, Edoardo
e7d094b2-e64f-4b4c-a452-d478a912b171
Janeczek, Agnieszka A.
71e60ef8-107b-44bd-9c0c-18d5e534ff21
Hailes, Alethia
7b0cacd6-8fac-4898-a925-4818a35abea0
de Andrés, Maria C.
54e87e8a-1aa2-4907-a8a0-25d0c15e5e40
De Grazia, Antonio
ca329577-0e10-424e-a104-af068c935f07
Oreffo, Richard OC
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Newman, Tracey A.
322290cb-2e9c-445d-a047-00b1bea39a25
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95

Scarpa, Edoardo, Janeczek, Agnieszka A., Hailes, Alethia, de Andrés, Maria C., De Grazia, Antonio, Oreffo, Richard OC, Newman, Tracey A. and Evans, Nicholas D. (2018) Polymersome nanoparticles for delivery of Wnt-activating small molecules. Nanomedicine: Nanotechnology, Biology, and Medicine, 14 (4), 1267-1277. (doi:10.1016/j.nano.2018.02.014).

Record type: Article

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.

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Accepted/In Press date: 24 February 2018
e-pub ahead of print date: 17 March 2018
Published date: 1 June 2018
Keywords: Drug delivery, Polymersomes, Wnt

Identifiers

Local EPrints ID: 421254
URI: http://eprints.soton.ac.uk/id/eprint/421254
ISSN: 1549-9634
PURE UUID: 192d20c2-c72b-4c06-a9ce-2f5671fb70db
ORCID for Agnieszka A. Janeczek: ORCID iD orcid.org/0000-0002-9745-8346
ORCID for Richard OC Oreffo: ORCID iD orcid.org/0000-0001-5995-6726
ORCID for Tracey A. Newman: ORCID iD orcid.org/0000-0002-3727-9258

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Date deposited: 29 May 2018 16:30
Last modified: 18 Feb 2021 16:54

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