title: Nanoparticles that communicate in vivo to amplify tumour targeting.
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.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: von Maltzahn
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Lin
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.forename: Christian
authors.initials: C
authors.lastname: Schwöppe
authors.forename: Rolf
authors.initials: R
authors.lastname: Mesters
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sailor
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001777:Blood Coagulation; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D008954:Models, Biological; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D015398:Signal Transduction; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides