This article provides a brief review of the literature on the interaction between synthetic particles and biomacromolecules. Understanding the nonspecific interactions between biomacromolecules and synthetic particles is of great importance for using materials in vitro and in vivo. The interaction between functionalized polymer particles and proteins has been studied extensively to identify the main factor that governs the interaction in vitro. Recently, the composition and properties of the protein corona that forms on the surface of nanoparticles (NPs) in biofluids have been studied in the context of the function and distribution of the particles in vivo. In the meantime, NPs that recognize specific biomacromolecules have also been designed by tuning the combination and distribution of functional groups on gold NPs and dendrimers. It has also been shown that nano-gel particles that recognize target molecules can be achieved by (A) optimizing the combination and amount of functional groups in the particles and (B) molecular imprinting polymerization, in combination with (C) affinity purification. Some of these particles are capable of recognizing target molecules and neutralizing their function, even in the bloodstream of living animals, as 'plastic antibodies.'

In this paper, a library of multi-functional linear poly-N-isopropylacrylamide (pNIPAm) polymers having a range of molecular weights and functional groups were synthesized and their interaction with the hemolytic peptide, melittin, was examined. The linear pNIPAm (LPs) containing both tert-butyl group and carboxylic acids bound with the peptide by a combination of hydrophobic and electrostatic interactions and neutralized its toxicity. The melittin binding capacity and affinity of each LP was quantified and further compared with cross-linked multi-functional nanogel particles (NPs) having same combination of functional groups. The binding capacity of the LPs (weight of captured melittin/weight of LP) was independent of their molecular weight and was three times higher than that of previously reported NPs.The binding constant depended on the molecular weight of the LPs, showing the highest value of 1.1 Â 10 8 (M À1 ) for a $1000 mer linear polymer with 40% tert-butyl group and 20% carboxylic acid.Comparison of the interactions of the LPs and NPs suggested the importance of the flexibility of the polymer chain in order to achieve high binding capacity and affinity.

Host-guest interactions between polyglycerol dendrimers of generations 3 and 4 (PGD-G3 and G4) and 4-amino-3-hydroxynapthalene-2-sulphonic acid (AHSA) were investigated by fluorescence spectroscopy, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS). PGD-G3 molecules were found to form an associated state with an average diameter of 82.7 nm in aqueous solution, in which PGD-G3 provided a much more polar microenvironment than glycerol. PGD-G3 and AHSA interacted attractively, showing a binding constant of 5.3×10(5)  M(-1) with a 2:1 stoichiometry. On the other hand, AHSA interacted with the periphery of PGD-G4, the majority of which existed as a unimer, forming a less polar microenvironment. The driving force of the interactions for PGD-G3 and -G4 were mainly enthalpically and entropically driven, respectively. The generation-dependent host-guest interactions were described in conjunction with thermodynamic parameters.

Synthetic polymer ligands (PLs) that recognize and neutralize specific biomacromolecules have attracted attention as stable substitutes for ligands such as antibodies and aptamers. PLs have been reported to strongly interact with target proteins and can be prepared by optimizing the combination and relative proportion of functional groups, by molecular imprinting polymerization, and/or by affinity purification. However, little has been reported about a strategy to prepare PLs capable of specifically recognizing a peptide from a group of targets with similar molecular weight and amino acid composition. In this study, we show that such PLs can be prepared by minimization of molecular weight and density of functional units. The resulting PLs recognize the target toxin exclusively and with 100-fold stronger affinity from a mixture of similar toxins. The target toxin is neutralized as a result. We believe that the minimization approach will become a valuable tool to prepare "plastic aptamers" with strong affinity for specific target peptides.

A polyglycerol dendrimer (PGD) of generation 2, which consists of only glycerol units, constructed nanospace capable of uptake of a fluorescent molecule with a 1:1 stoichiometry. On the other hand, a PGD of generation 1 trapped the molecule at the outer part.