Abstract
Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.
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Acknowledgements
This work was supported by the National Cancer Institute of the National Institutes of Health through grant numbers U54 CA 119335 (UCSD CCNE), 5-R01-CA124427 (Bioengineering Research Partnerships, BRP), U54 CA119349 (MIT CCNE) and 5 P30 CA30199-28 (SBMRI Cancer Center Support Grant). Work in the Muenster laboratory is supported by Deutsche Forschungsgemeinschaft (SFB 656/C8 Mesters) and German Cancer Aid (109245 Berdel). G.v.M. acknowledges support from Whitaker and NSF Graduate Fellowship. The authors thank P. Caravan for assistance with the fibrin-binding peptide selection and testing, D. Kim, S. Mo, L. Ong and M. Xu for assistance with in vivo studies and R. Weissleder for assistance with preliminary fluorescent imaging studies.
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G.v.M. and S.N.B. conceived the communication strategy, analysed results and wrote the manuscript; G.v.M., J-H.P., K.Y.L. and N.S. designed and carried out experiments; C.S., R.M., W.E.B., E.R. and M.J.S. contributed reagents and technical expertise.
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von Maltzahn, G., Park, JH., Lin, K. et al. Nanoparticles that communicate in vivo to amplify tumour targeting. Nature Mater 10, 545–552 (2011). https://doi.org/10.1038/nmat3049
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DOI: https://doi.org/10.1038/nmat3049
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