Applications brief: Folate-binding protein self-aggregation drives agglomeration of folic acid targeted iron oxide nanoparticles

Key results


  • A study on self-aggregating folate nanoparticles widely used for tumor targeting and drug delivery applications finds excess human serum albumin inhibits aggregation of particles ∼450 nm diameter but not of ∼40 nm diameter
  • Researchers employed Anasys afm to study folate particle morphology and measure the diameter of the agglomeration resulting from a triggered cascade


Key words

nanoIR | AFM | Folic acid | iron oxide | folate-conjugate | nanomaterials | nanoscience | nanoparticles

Authors

J. Chen, S. Klem, A. Jones, B. Orr, M. Banaszak Holl

Abstract

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 ggregated 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.


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AFM height image of an agglomerated FA conjugated iron oxide particle
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