title: Biomimetic amplification of nanoparticle homing to tumors.
abstract: Nanoparticle-based diagnostics and therapeutics hold great promise because multiple functions can be built into the particles. One such function is an ability to home to specific sites in the body. We describe here biomimetic particles that not only home to tumors, but also amplify their own homing. The system is based on a peptide that recognizes clotted plasma proteins and selectively homes to tumors, where it binds to vessel walls and tumor stroma. Iron oxide nanoparticles and liposomes coated with this tumor-homing peptide accumulate in tumor vessels, where they induce additional local clotting, thereby producing new binding sites for more particles. The system mimics platelets, which also circulate freely but accumulate at a diseased site and amplify their own accumulation at that site. The self-amplifying homing is a novel function for nanoparticles. The clotting-based amplification greatly enhances tumor imaging, and the addition of a drug carrier function to the particles is envisioned.
authors.affiliation: Cancer Research Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Simberg
authors.forename: Tasmia
authors.initials: T
authors.lastname: Duza
authors.forename: Ji Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Markus
authors.initials: M
authors.lastname: Essler
authors.forename: Jan
authors.initials: J
authors.lastname: Pilch
authors.forename: Lianglin
authors.initials: L
authors.lastname: Zhang
authors.forename: Austin M
authors.initials: AM
authors.lastname: Derfus
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Bhatia
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sailor
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D032701:Biomimetics / Q000379:methods*; D045744:Cell Line, Tumor; D008099:Liver / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis*; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology
chemical_list: D010455:Peptides