A magnetic switch for the control of cell death signalling i(4)

1042

NATURE MATERIALS |VOL 11|DECEMBER 2012|/naturematerials

© 2012 Macmillan Publishers Limited. All rights reserved

groups of zebrafish embryos show no apparent signals associated with active caspase-3(Fig.5e(i,ii)).In contrast,strong red spots associated with active caspase-3are clearly observed in the tail region for the magnetically activated group(Fig.5e(iii),f(iii)), which match closely with the region of green fluorescence signal of clustered zAb–MNPs.Note,the faint red signals seen for the control and non-activated groups in this immunostaining process are due to the naturally occurring mild apoptosis process of zebrafish(Fig.5f(i,ii)).The results of quantitative measurements of active caspase-3show that the magnetically activated group has an approximately6-fold higher fluorescence intensity level than those of the control and non-activated groups(Fig.5g).It has been documented that a bent tail is regarded as one of the most representative traits of apoptosis35,36.Consistent with this,the highly localized presence of OTR receptors,clustered MNPs and activated caspase-3in the lower part of the tail stem is likely to cause the tail to bend up through localized apoptotic cell death in the tail. The combined results demonstrate that the magnetic switch can be effectively applied to in vivo live vertebrates.

In the study described above,we have demonstrated that apoptosis signalling can be turned On in vitro and in a zebrafish in vivo model by using a magnetic switch.Our magnetic switch may be broadly applicable to any type of surface membrane receptors that exhibit cellular functions on clustering.With apoptosis being one of the main cancer research targets,the development of an extrinsic apoptosis agonist that can avoid p53mutation-induced drug resistance is important and here our magnetic switch can serve as a selective inducer19,27.Likewise,the applications can be extended to other clinically useful membrane receptors,such as the vascular endothelial growth factor receptor for regenerative medicine37and the Toll-like receptor for immune potentiation38.Although at an early stage of development,the spatially and temporally controlled magnetic switch system has the potential to be a useful tool for the activation of various cell signals at the target region.

Received20March2012;accepted23August2012;

published online7October2012

References

1.Hoffman,B.D.,Grashoff,C.&Schwartz,M.A.Dynamic molecular processes

mediate cellular mechanotransduction.Nature475,316–323(2011).

2.Gorostiza,P.&Isacoff,E.Y.Optical switches for remote and noninvasive

control of cell signaling.Science322,395–399(2008).

3.Lee,S.E.,Liu,G.L.,Kim,F.&Lee,L.P.Remote optical switch for localized

and selective control of gene interference.Nano Lett.9,562–570(2009).

4.Chung,I.et al.Spatial control of EGF receptor activation by reversible

dimerization on living cells.Nature464,783–787(2010).

5.Jang,J-t.et al.Critical enhancements of MRI contrast and hyperthermic

effects by dopant-controlled magnetic nanoparticles.Angew.Chem.Int.Ed.48, 1234–1238(2009).

6.Jordan,J.D.,Landau,E.M.&Iyengar,R.Signaling networks:The origins of

cellular multitasking.Cell103,193–200(2000).

7.Pankhurst,Q.A.,Connolly,J.,Jones,S.K.&Dobson,J.Application of

magnetic nanoparticles in biomedicine.J.Phys.D36,R167–R181(2003).

8.Gupta,A.K.&Gupta,M.Synthesis and surface engineering of iron oxide

nanoparticles for biomedical applications.Biomaterials26,3995–4021(2005).

9.Huang,H.,Delikanli,S.,Zeng,H.,Ferkey,D.M.&Pralle,A.Remote control

of ion channels and neurons through magnetic-field heating of nanoparticles.

Nature Nanotech.5,602–606(2010).

10.Creixell,M.et al.EGFR-targeted magnetic nanoparticle heaters kill cancer cells

without a perceptible temperature rise.ACS Nano5,7124–7129(2011).

11.Wang,N.,Butler,J.P.&Ingber,D.E.Mechanotransduction across the cell

surface and through the cytoskeleton.Science260,1124–1127(1993).

12.Kanczler,J.M.et al.Controlled differentiation of human bone marrow

stromal cells using magnetic nanoparticle technology.Tissue Eng.16,

3241–3250(2010).

13.Hughes,S.,Haj,A.J.E.&Dobson,J.Magnetic micro-and nanoparticle

mediated activation of mechanosensitive ion channels.Med.Eng.Phys.27, 754–762(2005).

14.Dobson,J.Remote control of cellular behavior with magnetic nanoparticles.

Nature Nanotech.3,139–143(2008).15.Mannix,R.J.et al.Nanomagnetic actuation of receptor-mediated signal

transduction.Nature Nanotech.3,36–40(2008).

16.Lee,J-H.et al.Artificial control of cell signaling and growth by magnetic

nanoparticles.Angew.Chem.Int.Ed.49,5698–5702(2010).

17.Danial,N.N.&Korsmeyer,S.J.Cell death:Critical control points.Cell116,

205–219(2004).

18.Williams,G.T.Programmed cell death:Apoptosis and oncogenesis.Cell65,

1097–1098(1991).

19.Storey,S.Targeting apoptosis:Selected anticancer strategies.Nature Rev.7,

百度搜索“77cn”或“免费范文网”即可找到本站免费阅读全部范文。收藏本站方便下次阅读，免费范文网，提供经典小说公务员考试A magnetic switch for the control of cell death signalling i(4)在线全文阅读。