A novel method for preparation of biomacromolecular imprinted nanoparticles is described. Combinations of functional monomers were polymerized in the presence of the imprinting peptide melittin in aqueous solution at room temperature to produce a small library of polymer nanoparticles. The template peptide and unreacted monomers are subsequently removed by dialysis. Nanoparticles (NPs) from the library were evaluated for their binding to melittin by 27 MHz QCM analysis. NPs prepared with optimized functional monomer combinations bind strongly to the target molecule. Nanoparticles that were polymerized in the absence of template peptide were found to have little affinity to the peptide. Binding affinity and the size of imprinted particles are comparable to those of natural antibodies. They interact specifically with the target peptide and show little affinity for other proteins. These NPs are of interest as inert and stable substitutes for antibodies. Extension of this approach to other targets of biological importance and the applications of these materials are currently being evaluated.

We report that simple, synthetic organic polymer nanoparticles (NPs) can capture and clear a target peptide toxin in the bloodstream of living mice. The protein-size polymer nanoparticles, with a binding affinity and selectivity comparable to natural antibodies, were prepared by combining a functional monomer optimization strategy with molecular imprinting nanoparticle synthesis. As a result of binding and removal of melittin by NPs in vivo, mortality and peripheral toxic symptoms of melittin were significantly diminished. In vivo imaging of the polymer nanoparticles or "plastic antibodies" establishes the NPs accelerate clearance of the peptide from blood where they accumulate in the liver. Coupled with their biocompatibility and nontoxic characteristics, plastic antibodies offer potential for neutralizing a wide range of biomacromolecules in vivo.In nature, antibodies recognize target molecules by a combination of multiple weak electrostatic, hydrophobic and hydrogen bonding interactions between complementary threedimensional surfaces. To mimic these interactions, nanoparticles (NPs) with affinity for a target peptide or protein have been synthesized by optimizing the composition and ratio of functional groups that make up the NPs.1 , 2 However, the specificity and affinity of the random yhoshino@uci.edu; kjshea@uci.edu. Supporting Information Available: Experimental procedures and supporting data. This material is available free of charge via the Internet at http://pubs.acs.org. We have developed methods for synthesizing protein-size polymer particles with a binding affinity and selectivity comparable to natural antibodies by combining molecular imprinting nanoparticle synthesis with a functional monomer optimization strategy (Figure 1).9 The first stage of this process involves screening small libraries of NPs that span a compositional space chosen for its complementarity to the biological target. 2 The affinity of each NP to the biological target is evaluated and the composition of subsequent NP generations is adjusted to enhance specificity. At the final stage the optimized combination and ratio of functional monomers are polymerized in the presence of the imprinting biological target (peptide or epitope). 9 Following extensive dialysis, polymer NPs exhibit binding affinity, selectivity and particle size comparable to natural antibodies in vitro. NIH Public AccessAlthough molecular recognition by imprinted materials has been extensively studied in controlled settings, little is reported about their application in the bloodstream of living animals. 10 It is well known that the performance (affinity, specificity and function) of synthetic materials when introduced into a complex biological milieu can be profoundly compromised. Introduction of foreign substances including synthetic NPs into the bloodstream results in the immediate formation of a "corona" of proteins on the surface that can alter and/or suppress the intended function of the NP. 11 Further complications can arise fron an immunogenic re...

Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.

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.

We report that multi functional polymer nanoparticles approximately the size of a large protein can be "purified", on the basis of peptide affinity just as antibodies, using an affinity chromatography strategy. The selection process takes advantage of the thermo-responsiveness of the nanoparticles allowing "catch and release" of the target peptide by adjusting the temperature. Purified particles show much stronger affinity (Kd app ≈ nM) and a narrower affinity distribution than the average of particles before purification (Kd app > μM) in room temperature, but can release the peptide just by changing temperature. We anticipate this affinity selection will be general and become an integral step for the preparation of "plastic antibodies" with near homogeneous and tailored affinity for target biomacromolecules.General procedures for the creation of synthetic materials with biomacromolecular recognition sites are of significant interest as a route to stable, robust and mass-produced substitutes for antibodies. [1][2][3][4][5][6][7][8] Ideally, recognition of complex biological targets, including proteins, peptides and carbohydrates, requires multiple functional groups that contact target molecules by a combination of electrostatic, hydrogen-bonding, van der Waals, and/or hydrophobic interactions. It has been shown that copolymerization of optimized combinations and ratios of functional monomers creates synthetic polymer materials with molecular recognition sites. [1][2][3][4][5] However, in contrast to antibodies whose exact sequence can be determined and cloned, polymerized materials result in heterogeneous structures with a distribution of recognition sites. 1,3,7 This is an intrinsic property of polymers synthesized under kinetic control, in contrast to the synthetic small molecular hosts prepared by multi step reactions 9 or by self-assembly under equilibrating conditions 10 . Here we demonstrate a general procedure to purify synthetic polymer nanoparticles (NPs) with high-affinity binding sites for a target biomacromolecule from a random pool of multi-functional copolymer nanoparticles (MFNPs). These nanoparticles are approximately the size of a large protein and are "purified" on the basis of peptide affinity just as antibodies, using an affinity chromatography strategy. The concept of affinity purification of NPs was demonstrated with melittin, a 26 amino acid peptide ( fig. 1a), as the target molecule. Melittin has six positive charges of which four are localized in a hydrophilic six amino acid sequence on the C-terminus. The remaining twenty amino acids have a high proportion of apolar residues. 11For the MFNPs, we chose cross-linked N-isopropylacrylamide NPs (~30 nm) incorporating hydrophobic (N-t-butylacrylamide (TBAm)) and negatively charged (acrylic acid (AAc)) functional monomers ( fig. 1b). We have reported that NPs with this composition interacts with melittin (K dapp = 46 μM) via both electrostatic-and hydrophobi nteractions in PBS (35mM phosphate buffer/0.15 M NaCl, pH 7.3). 5 However, th...

The potential impact of encapsulated molecules on the thermal properties of individual carbon nanotubes (CNTs) has been an important open question since the first reports of the strong modulation of electrical properties in 2002. However, thermal property modulation has not been demonstrated experimentally because of the difficulty of realizing CNT-encapsulated molecules as part of thermal transport microstructures. Here we develop a nanofabrication strategy that enables measurement of the impact of encapsulation on the thermal conductivity (κ) and thermopower (S) of single CNT bundles that encapsulate C , Gd@C and Er @C. Encapsulation causes 35-55% suppression in κ and approximately 40% enhancement in S compared with the properties of hollow CNTs at room temperature. Measurements of temperature dependence from 40 to 320 K demonstrate a shift of the peak in the κ to lower temperature. The data are consistent with simulations accounting for the interaction between CNTs and encapsulated fullerenes.

Porous metals are used in interfacial transport applications that leverage the combination of electrical and/or thermal conductivity and the large available surface area. As nanomaterials push toward smaller pore sizes to increase the total surface area and reduce diffusion length scales, electron conduction within the metal scaffold becomes suppressed due to increased surface scattering. Here we observe the transition from diffusive to quasi-ballistic thermal conduction using metal inverse opals (IOs), which are metal films that contain a periodic arrangement of interconnected spherical pores. As the material dimensions are reduced from ∼230 nm to ∼23 nm, the thermal conductivity of copper IOs is reduced by more than 57% due to the increase in surface scattering. In contrast, nickel IOs exhibit diffusive-like conduction and have a constant thermal conductivity over this size regime. The quasi-ballistic nature of electron transport at these length scales is modeled considering the inverse opal geometry, surface scattering, and grain boundaries. Understanding the characteristics of electron conduction at the nanoscale is essential to minimizing the total resistance of porous metals for interfacial transport applications, such as the total electrical resistance of battery electrodes and the total thermal resistance of microscale heat exchangers.

The ability to efficiently and reliably transfer heat between sources and sinks is often a bottleneck in the thermal management of modern energy conversion technologies ranging from microelectronics to thermoelectric power generation. These interfaces contribute parasitic thermal resistances that reduce device performance and are subjected to thermomechanical stresses that degrade device lifetime. Dense arrays of vertically aligned metal nanowires (NWs) offer the unique combination of thermal conductance from the constituent metal and mechanical compliance from the high aspect ratio geometry to increase interfacial heat transfer and device reliability. In the present work, we synthesize copper NW arrays directly onto substrates via templated electrodeposition and extend this technique through the use of a sacrificial overplating layer to achieve improved uniformity. Furthermore, we infiltrate the array with an organic phase change material and demonstrate the preservation of thermal properties. We use the 3ω method to measure the axial thermal conductivity of freestanding copper NW arrays to be as high as 70 W m(-1) K(-1), which is more than an order of magnitude larger than most commercial interface materials and enhanced-conductivity nanocomposites reported in the literature. These arrays are highly anisotropic, and the lateral thermal conductivity is found to be only 1-2 W m(-1) K(-1). We use these measured properties to elucidate the governing array-scale transport mechanisms, which include the effects of morphology and energy carrier scattering from size effects and grain boundaries.