Folate-Binding Protein Self-Aggregation Drives Agglomeration of Folic Acid Targeted Iron Oxide Nanoparticles

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• 作者：Junjie Chen ; Sarah Klem ; Alexis K. Jones ; Bradford Orr ; Mark M. Banaszak Holl
• 刊名：Bioconjugate Chemistry
• 出版年：2017
• 出版时间：January 18, 2017
• 年：2017
• 卷：28
• 期：1
• 页码：81-87
• 全文大小：386K
• ISSN：1520-4812

文摘

Folate-conjugated nanomaterials have been widely investigated for drug and imaging-agent delivery. In this work, two folic acid (FA) conjugated iron oxide particles (IOP), a ∼40 nm diameter FA–IOP and a ∼450 nm diameter FA–IOP(FA–SeraMag), were synthesized. Both particles aggregated in the presence of serum folate-binding protein (FBP) at physiological concentration and buffer conditions. Mixing 0.01% w/w FA-conjugated iron oxide particles with FBP-induced agglomeration generated an average hydrodynamic particle diameter of 3800 ± 1100 nm for ∼40 nm FA–IOP and 4030 ± 1100 nm for FA–SeraMag as measured by dynamic light scattering (DLS). The presence of excess human serum albumin (HSA) (600 μM) did not prevent agglomeration of the ∼40 nm FA–IOP; however, it did inhibit agglomeration of FA–SeraMag. Atomic force microscopy measurement provided additional insight into particle morphology with the detection of individual particles in the agglomerate. This behavior is an example of a triggered cascade. A protein structural change is induced by FA binding, and the structural change favors aggregation of the ∼4 nm diameter FBPs on the particle surface; this further triggers the agglomeration of both the ∼40 and ∼450 nm diameter IOPs.