Nanoparticles that communicate in vivo to amplify tumour targeting

Author Manuscript: 2012 May 29Nanomedicines 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.National Cancer Institute (U.S.) (SBMRI Cancer Center Support Grant 5 P30 CA30199-28)National Cancer Institute (U.S.) (MIT CCNE Grant U54 CA119349)National Cancer Institute (U.S.) (Bioengineering Research Partnership Grant 5-R01-CA124427)National Cancer Institute (U.S.) (UCSD CCNE Grant U54 CA 119335)National Science Foundation (U.S.) (Whitaker Graduate Fellowship

Strategies for site-specific protein biotinylation using in vitro, in vivo and cell-free systems: Toward functional protein arrays

10.1038/nprot.2006.338Nature Protocols152386-239