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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
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