Different Effect of Hydrogelation on Antifouling and Circulation Properties of Dextran鈥揑ron Oxide Nanoparticles
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- 作者：Priya Prakash Karmali ; Ying Chao ; Ji-Ho Park ; Michael J. Sailor ; Erkki Ruoslahti ; Sadik C. Esener ; Dmitri Simberg
- 刊名：Molecular Pharmaceutics
- 出版年：2012
- 出版时间：March 5, 2012
- 年：2012
- 卷：9
- 期：3
- 页码：539-545
- 全文大小：344K
- 年卷期：v.9,no.3(March 5, 2012)
- ISSN：1543-8392
文摘
Premature recognition and clearance of nanoparticulate imaging and therapeutic agents by macrophages in the tissues can dramatically reduce both the nanoparticle half-life and delivery to the diseased tissue. Grafting nanoparticles with hydrogels prevents nanoparticulate recognition by liver and spleen macrophages and greatly prolongs circulation times in vivo. Understanding the mechanisms by which hydrogels achieve this 鈥渟tealth鈥?effect has implications for the design of long-circulating nanoparticles. Thus, the role of plasma protein absorption in the hydrogel effect is not yet understood. Short-circulating dextran-coated iron oxide nanoparticles could be converted into stealth hydrogel nanoparticles by cross-linking with 1-chloro-2,3-epoxypropane. We show that hydrogelation did not affect the size, shape and zeta potential, but completely prevented the recognition and clearance by liver macrophages in vivo. Hydrogelation decreased the number of hydroxyl groups on the nanoparticle surface and reduced the binding of the anti-dextran antibody. At the same time, hydrogelation did not reduce the absorption of cationic proteins on the nanoparticle surface. Specifically, there was no effect on the binding of kininogen, histidine-rich glycoprotein, and protamine sulfate to the anionic nanoparticle surface. In addition, hydrogelation did not prevent activation of plasma kallikrein on the metal oxide surface. These data suggest that (a) a stealth hydrogel coating does not mask charge interactions with iron oxide surface and (b) the total blockade of plasma protein absorption is not required for maintaining iron oxide nanoparticles鈥?long-circulating stealth properties. These data illustrate a novel, clinically promising property of long-circulating stealth nanoparticles.