Design of Synthetic Polymer Nanoparticles that Capture and Neutralize a Toxic Peptide

Abstract

Designed polymer nanoparticles (NPs) capable of binding and neutralizing a biomacromolecular toxin are prepared. A library of copolymer NPs is synthesized from combinations of functional monomers. The binding capacity and affinity of the NPs are individually analyzed. NPs with optimized composition are capable of neutralizing the toxin even in a complex biological milieu. It is anticipated that this strategy will be a starting point for the design of synthetic alternatives to antibodies.

The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo

“…The neutralization efficiency of melittin by NPs 1-6 was tested by the red blood cell lyses test. As we reported, NPs with both carboxylic acid (AAc) and t-butyl groups (TBAm) (NPs 4) significantly neutralized melittin (6). Melittin is comprised primarily of positively charged and hydrophobic amino acids.…”

“…Previously, we have shown that copolymer NPs consisting of random distributions of both hydrophobic and negatively charged monomers captures the peptide toxin melittin by both hydrophobic and electrostatic interactions (6). However, the combined affinity and specificity of the NPs were not sufficient to detoxify melittin in animal models.…”

“…In an effort to mimic these interactions, bulk polymer materials that capture target molecules by multipoint interactions have been synthesized by incorporating moderate amounts of functional monomers that interact with target molecules primarily by electrostatic interactions (5). Nano-size materials with affinity for a target peptide or protein have also been synthesized by optimizing the composition and/or ratio of functional groups on the surface of the synthetic NPs (6). Some success was achieved by a judicious choice of ligands used to coat gold NPs or by stabilizing charged groups on dendritic polymers (7,8).…”

“…Linear polyacrylamides that are functionalized with arginine receptors have also been shown to interact with arginine-rich proteins (9). It has also been demonstrated that polymer NPs synthesized with an optimized combination of functional monomers can capture target molecules (10) and neutralize its function (6). However, little has been reported about a general design rationale for achieving NPs with molecular recognition for in vivo applications (3,8).…”

Preparation of nanogel-immobilized porous gel beads for affinity separation of proteins: fusion of nano and micro gel materials

“…Figure 3e and f indicate that the surface morphology of the pore structures after adsorption of the NPs were less angulated than the surface morphology before adsorption, although none of the pores were filled by the NPs. The apparent surface roughness of the NPs-immobilized pore surface seemed to be comparable to that of the mono-layered dried NPs films (o10 nm), 10,19,20 suggesting that the surface of GBs were coated with NPs. From those results, it was established that NP-adsorbed macroporous GBs could be prepared simply by incubating negatively charged NPs and positively charged GBs in water.…”