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Biomimetic amplification of nanoparticle homing to tumors

Simberg, Dmitri, Duza, Tasmia, Park, Ji Ho, Essler, Markus, Pilch, Jan, Zhang, Lianglin, Derfus, Austin M., Yang, Meng, Hoffman, Robert M., Bhatia, Sangeeta, Sailor, Michael J., Ruoslahti, Erkki
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.3 pp. 932-936
binding sites, biomimetics, blood proteins, diagnostic techniques, drug carriers, image analysis, iron oxides, nanoparticles, neoplasms
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.