Biomimetic amplification of nanoparticle homing to tumors

被引:376
作者
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
机构
[1] Burnham Inst Med Res, Canc Res Ctr, La Jolla, CA 92037 USA
[2] Univ Calif Santa Barbara, Burnham Inst Med Res, Santa Barbara, CA 93106 USA
[3] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Mat Sci & Engn Program, La Jolla, CA 92093 USA
[5] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
[6] AntiCanc Inc, San Diego, CA 92111 USA
[7] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA
[8] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[9] Brigham & Womens Hosp, MIT, Dept Elect Engn & Comp Sci, Boston, MA 02115 USA
关键词
clotting; liver; peptide; tumor targeting; iron oxide;
D O I
10.1073/pnas.0610298104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:932 / 936
页数:5
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