Molecularly Imprinted Nanoparticles Research Articles

3D BIOMIMETIC CONSTRUCTS STEER STEM CELL COMMITMENT BY SYNERGISTIC MODULATION OF BIOPHYSICAL CUES AND GROWTH FACTOR SIGNALLING

Tendon diseases are prevalent health concerns for which current therapies present limited success, in part due to the intrinsically low regenerative ability of tendons. Therefore, tissue engineering presents a potential to improve this outcome. Here, we hypothesize that a concurrent control over both biophysical and biochemical stimuli will boost the tenogenic commitment of stem cells, thus promoting regeneration. To achieve this, we combine molecularly imprinted nanoparticles (MINPs), which act as artificial amplifiers for endogenous growth factor (GF) activity, with bioinspired anisotropic hydrogels2 to manufacture 3D tenogenic constructs. MINPs were solid phase-imprinted using a TGF-β3 epitope as template and their affinity for the target was assessed by SPR and dot blot. Magnetically-responsive microfibers were produced by cryosectioning electrospun meshes containing iron oxide nanoparticles. The constructs were prepared by encapsulating adipose tissue-derived stem cells (ASCs), microfibers, and MINPs within gelatin hydrogels, while aligning the microfibers with an external magnetostatic field during gelation. This allows an effective modulation of hydrogel fibrillar topography, mimicking the native tissue's anisotropic architecture. Cell responses were analyzed by multiplex immunoassay, quantitative polymerase chain reaction, and immunocytochemistry. MINPs showed an affinity for the template comparable to monoclonal antibodies. Encapsulated ASCs acquired an elongated shape and predominant orientation along the alignment direction. Cellular studies revealed that combining MINPs with aligned microfibers increased TGF-β signaling via non-canonical Akt/ERK pathways and upregulated tendon-associated gene expression, contrasting with randomly oriented gels. Immunostaining of tendon-related proteins presented analogous outcomes, corroborating our hypothesis.Our results thus demonstrate that microstructural cues and biological signals synergistically direct stem cell fate commitment, suggesting that this strategy holds potential for improving tendon healing and might be adaptable for other biological tissues. The proposed concept highlights the GF-sequestering ability of MINPs which allows a cost-effective alternative to recombinant GF supplementation, potentially decreasing the translational costs of tissue engineering strategies.Acknowledgements: The authors acknowledge the funding from the European Union's Horizon 2020 under grant No. 772817; from FCT/MCTES for scholarships PD/BD/143039/2018 & COVID/BD/153025/2022 (S.P.B.T.), and PD/BD/129403/2017 (S.M.B.), co-financed by POCH and NORTE 2020, under the Portugal 2020 partnership agreement through the European Social Fund, for contract 2020.03410.CEECIND (R.M.A.D.) and project 2022.05526.PTDC; and from Xunta de Galicia for grant ED481B2019/025 (A.P.).

Molecularly imprinted nanoparticles reveal regulatory scaffolding features in Pyk2 tyrosine kinase.

Pyk2 is a multi-domain non-receptor tyrosine kinase that serves dual roles as a signaling enzyme and scaffold. Pyk2 activation involves a multi-stage cascade of conformational rearrangements and protein interactions initiated by autophosphorylation of a linker site. Linker phosphorylation recruits Src kinase, and Src-mediated phosphorylation of the Pyk2 activation loop confers full activation. The regulation and accessibility of the initial Pyk2 autophosphorylation site remains unclear. We employed peptide-binding molecularly imprinted nanoparticles (MINPs) to probe the regulatory conformations controlling Pyk2 activation. MINPs differentiating local structure and phosphorylation state revealed that the Pyk2 autophosphorylation site is protected in the autoinhibited state. Activity profiling of Pyk2 variants implicated FERM and linker residues responsible for constraining the autophosphorylation site. MINPs targeting each Src docking site disrupt the higher-order kinase interactions critical for activation complex maturation. Ultimately, MINPs targeting key regulatory motifs establish a useful toolkit for probing successive activational stages in the higher-order Pyk2 signaling complex.

Synthesis and Evaluation of Molecularly Imprinted Nanoparticles for Detection and Quantification of Zolpidem In Human Plasma

AbstractIn response to the alarming rates of zolpidem abuse, this study presents a pioneering approach utilizing molecularly imprinted nanoparticles (MIPs) in conjunction with high‐performance liquid chromatography (HPLC) for the selective detection of zolpidem. The rational choice of zolpidem as the target analyte stems from its widespread misuse and clinical significance. The MIPs were prepared using the precipitation polymerization method, resulting in monodispersed nanoparticles with a size of approximately 258.8 nm. Fourier Transform Infrared (FTIR) analysis confirmed the successful incorporation of zolpidem into the MIPs, designed with tailored cavities for zolpidem recognition. Moreover, incorporating the bathochromic shift phenomenon reaffirms the successful imprinting procedure. The rebinding studies showed that MIPs were highly efficient in adsorbing zolpidem from the solvent, with more than 95 % of the drug recovered after multiple cycles. The selectivity study demonstrated the MIPs′ preference for zolpidem over another drug, diazepam. The MIPs′ successful separation of zolpidem from spiked human plasma samples further validates their potential for practical applications, such as clinical toxicology. This research showcases the potential of MIPs coupled with HPLC as a powerful tool for accurate zolpidem quantification, holding great promise for combating drug abuse and advancing analytical methodologies for pharmaceutical analysis.

Isoform-specific recognition of phosphopeptides by molecular imprinting nanoparticles with double-binding mode

Phosphorylation is one of the most important post-translational modifications of proteins, but due to the low abundance of phosphopeptides, enrichment is an essential step before mass spectrometric analysis. Although there are a number of enrichment methods developed targeting different forms of proteins phosphorylations, there are few reports on specific recognition and capture of single phosphopeptide. Herein, based on the advantages of dual affinity of TiO2 and urea to a phosphate group and molecular imprinting towards the peptide sequence, the precise recognition of intact phosphorylated peptides was successfully achieved. The same peptide sequence with different phosphorylation forms (c.a. Ser, Thr and Tyr) were used as templates for proof-of-principle study, and the imprinted particles were successfully synthesized, characterized, and have the capacity to specifically recognize the targeted unique phosphorylation excluding even its isoforms. In addition, the produced molecularly imprinted nanoparticles have numerous important advantages, including strong affinity, high specificity toward single phosphopeptides, tolerance to interferences, fast binding kinetics, substantial binding capacity, excellent stability and reusability, making them an ideal sorbent for specific enrichment of unique phosphopeptides. Finally, different phosphorylation forms were specifically enriched from both standard peptides’ mixture and casein/milk digests.

Environmental modulation of chiral prolinamide catalysts for stereodivergent conjugate addition

Synthetic chiral catalysts generally rely on proximal functional groups or ligands for chiral induction. Enzymes often employ environmental chirality to achieve stereoselectivity. Environmentally controlled catalysis has benefits such as size and shape selectivity but is underexplored by chemists. We here report molecularly imprinted nanoparticles (MINPs) that utilized their environmental chirality to either augment or reverse the intrinsic selectivity of a chiral prolinamide cofactor. The latter ability allowed the catalyst to produce products otherwise disfavored in the conjugate addition of aldehyde to nitroalkene. The catalysis occurred in water at room temperature and afforded γ-nitroaldehydes with excellent yields (up to 94%) and ee (>90% in most cases). Up to 25:1 syn/anti and 1:6 syn/anti ratios were achieved through a combination of catalyst-derived and environmentally enabled selectivity. The high enantioselectivity of the MINP also made it possible for racemic catalysts to perform asymmetric catalysis, with up to 80% ee for the conjugate addition.

Fluorescence detection of carbofuran in aqueous extracts based on dual-emission SiO2 @Y2 O3 :(Eu3+ ,Tb3+ )@MIP core-shell structural nanoparticles.

A novel double-windows fluorescence sensor for carbofuran (CF) detection was successfully developed based on rare-earth Eu,Tb-doped Y2 O3 @SiO2 -based molecularly imprinted nanoparticles (MINs) with a multilayer core-shell structure. The recognition process of the MINs for CF was fairly fast and needed only ~8 min to reach a dynamic equilibrium. Interestingly, one fluorescence attenuation window was found with an increase in CF concentration (Q) from 0.1 to 10 μg ml-1 and with a limit of detection (LOD) of 0.04 μg ml-1 at 544 nm belonging to the Tb3+ emission, as well as another fluorescence enhanced window within the CF concentration range 10-100 μg ml-1 (LOD = 4 μg ml-1 ) at 617 nm of Eu3+ emission in the dispersed rare-earth-doped MIN colloidal aqueous solution. Luminescence resonance energy transfer from CF to Eu3+ and an inner filter effect of CF towards Tb3+ , as well from the two independent detection windows were clearly observed simultaneously. The competition experiment displayed hardly any marked interference during detection of CF following addition of its analogues (carbaryl, isoprocarb, aldicarb, methomyl, and etofenprox). Moreover, the MINs could also be applied to accurately detect CF in rhubarb and wolfberry samples with recoveries of 85.7-92.2%. This sensing system has high specific recognition and a wide detection range for CF and provides new opportunities for pesticide detection.

One-Pot Strategy as a Green and Rapid Method to Fabricate Magnetic Molecularly Imprinted Nanoparticles for Selective Capture of Sulfonylurea Herbicides.

Magnetic solid-phase extraction (MSPE) based on molecularly imprinted nanoparticles (MINs) has attracted wide attention in sample pretreatment because it combines the merits of high selectivity and quick extraction procedures. However, laborious, time and solvent-consuming steps were involved in the synthesis of magnetic imprinted particles in existing approaches. To circumvent this dilemma, a green and rapid "one-pot" strategy was proposed to prepare MINs. Halosulfuron-methyl (HSM) was selected as a template molecule, and Gaussian 09 simulation software was employed to screen the 2,4,6-trivinylboroxin pyridine complex (TBP) as a functional monomer. Subsequently, the fabrication was simply conducted using a hydrothermal approach by mixing self-assembly solution of TBP-HSM, Fe3+, Fe2+, dimethyl sulfoxide, and azobisisobutyronitrile in one-pot with a total reaction time of 3.0 h. Various characterized results well evidenced the successful imprint of HSM and the resultant HSM-MINs presented satisfying superparamagnetism and saturation magnetism. Under the optimized parameters, the obtained HSM-MINs displayed good recognition capability and selectivity toward HSM (recognition coefficient was 2.60), as well as a satisfactory saturation adsorption capacity (1781 μg/g). The quantification of sulfonylurea herbicides at trace levels in environmental water and soil samples was selected as a paradigm to demonstrate the practicality and reliability of HSM-MINs/MSPE. The present study provides a convenient, reliable, and green approach for fabricating a magnetic molecular-imprinting adsorbent for MSPE.

Synthesis and evaluation of mesoporous silica/mesoporous molecularly imprinted nanoparticles as adsorbents for detection and selective removal of imidacloprid in food samples

The double-mesoporous-layer imprinted polymer of mesoporous silica/mesoporous molecularly imprinted nanoparticles (MIP), with high specific surface area, rich porosity, excellent mass transfer rate and selectivity, were synthesized using imidacloprid (IDP) as a template. Under the optimal conditions of pH, contact time, concentration and temperature, MIP showed high adsorption capacity of 13.86 μg·mg−1 toward IDP and the imprinting factor reached 3.5. The adsorption process model including binding isotherm and kinetics was investigated. MIP exhibited excellent regeneration and its adsorption and selectivity were outstanding among its structurally pesticide analogues. The recovery of spiked IDP for MIP in fortified real samples can reach 96.0 ± 8.5% for cabbage and 105.0 ± 9.9% for apple. The limit of detection of the enrichment method can be as low as 0.037 μg·mL-1 with a good linear relationship (R2 = 0.996) from 0.30 to 10.0 μg·mL−1. The results indicated that the proposed method allowed class-specific detection of IDP in food samples.

Epitope‐Imprinted Nanoparticles as Transforming Growth Factor‐β3 Sequestering Ligands to Modulate Stem Cell Fate

AbstractGrowth factors (GFs) are biomolecules with potent biological effects but inherent limitations hinder their potential as therapeutic agents and cell culture supplements in tissue engineering and regenerative medicine (TERM). Biomaterials that sequester endogenous GFs by affinity binding might circumvent such limitations and thus are being increasingly investigated. Here, molecularly imprinted nanoparticles (MINPs) are proposed as specific abiotic ligands for GFs. As a proof of concept, a conformational epitope of transforming growth factor‐β3 (TGF‐β3) is designed and surface imprinted onto polyacrylamide‐based nanoparticles by inverse microemulsion polymerization. It is found that, depending on the polymerization mixture composition, MINPs can recognize and preferentially bind TGF‐β3, either in noncompetitive assays or from a complex human fluid (platelet lysate). Substrates functionalized with MINPs are then used for 2D culture of adipose‐derived stem cells. Remarkably, gene and protein expression profiles show a marked upregulation of SOX‐9, suggesting activation of TGF‐β3 signaling pathways without requiring supplementation with exogenous GF. Likewise, culturing these cells in pellets incorporating MINPs previously incubated with platelet lysate results in higher collagen II‐rich matrix deposition, compared to pellets incorporating non‐imprinted nanoparticles. In summary, results suggest MINPs can be used as cost‐effective, stable, and scalable alternative abiotic GF ligands to guide cell fate in TERM applications.

Polymeric nanoparticles for selective protein recognition by using thiol-ene miniemulsion photopolymerization

The fabrication of molecularly imprinted nanoparticles (MIP-NPs) specific for myoglobin by using thiol-ene photopolymerization in miniemulsion was described. Allyl derivatives of phenylalanine as a functional monomer was synthesized and copolymerized with acrylic monomers via miniemulsion polymerization to produce NIP-NPs with approximately 74 nm number average particle diameter. FTIR and 1H-NMR analysis confirmed the synthesis of functional monomer. MIP-NPs were prepared in the existence of myoglobin as a template protein. Morphological investigations exhibited that the particle size of the MIP-NPs, increased compared to the corresponding NIPs and the mean particle diameter by number was measured as 141 nm with narrow distribution. NIP-NPs that were polymerized without myoglobin were found to have less affinity to the target protein. In addition, the rebinding ability of MIP-NPs was much bigger than that of the corresponding NIPs. ELISA results showed that MIPs interact particularly with the myoglobin and show little affinity for BSA in competitive binding experiments.HighlightsAllyl N,N-diallyl phenylalaninate was synthesized as a functional monomer.Imprinted nanoparticles were prepared by using thiol-ene photopolymerization in miniemulsion.The nanoparticles were 141 nm with narrow size distribution.The imprinted nanoparticles showed selectivity toward myoglobin.

Construction of molecularly imprinted nanoparticles by employing ultrasound waves for selective determination of doxepin from human plasma samples: Modeling and optimization.

In this work, molecularly imprinted nanoparticles (MINPs) were applied as selective adsorbent for ultrasound-assisted micro-solid-phase extraction (UAMSPE) of doxepin (DP) from human plasma samples, which was then cleaned up, pre-concentrated and subjected to HPLC. The MINPs were synthesized based on a non-covalent approach by precipitation polymerization utilizing methacrylic acid and styrene as functional monomers, DP as template, ethylene glycol dimethacrylate as cross-linker and 2,2-azobisisobutyronitrile (AIBN) as initiator. The obtained MINPs were characterized by Fourier transform-infrared and field emission scanning electron microscopy. Factors influencing the efficiency of UAMSPE such as sonication time, volume of eluent solvent and amount of sorbent were investigated using a central composite design and the optimal points were identified as 4 min of sonication time, 380 μL of eluent solvent and 30 mg of sorbent. Under optimized conditions, the proposed method has linear responses in the range of 0.2-2000 ng mL-1 , with a satisfactory limit of detection of 0.04 ng mL-1 and limit of quantification of 0.11 ng mL-1 .

Tuning surface-cross-linking of molecularly imprinted cross-linked micelles for molecular recognition in water.

Molecular recognition in water is an important challenge in supramolecular chemistry. Surface-core double cross-linking of template-containing surfactant micelles by the click reaction and free radical polymerization yields molecularly imprinted nanoparticles (MINPs) with guest-complementary binding sites. An important property of MINP-based receptors is the surface-cross-linking between the propargyl groups of the surfactants and a diazide cross-linker. Decreasing the number of carbons in between the two azides enhanced the binding affinity of the MINPs, possibly by keeping the imprinted binding site more open prior to the guest binding. The depth of the binding pocket can be controlled by the distribution of the hydrophilic/hydrophobic groups of the template and was found to influence the binding in addition to electrostatic interactions between oppositely charged MINPs and guests. Cross-linkers with an alkoxyamine group enabled two-stage double surface-cross-linking that strengthened the binding constants by an order of magnitude, possibly by expanding the binding pocket of the MINP into the polar region. The binding selectivity among very similar isomeric structures also improved.

Sequence-Selective Recognition of Peptides in Aqueous Solution: A Supramolecular Approach through Micellar Imprinting.

Sequence-selective recognition of peptides in water has been one of the most important and yet unsolved problems in bioorganic and supramolecular chemistry. The motivation comes from not only the importance of these molecules in biology but also the fundamental challenges involved in the research. Molecular imprinting in doubly cross-linked surfactant micelles offers a unique solution to this problem by creating a "supramolecular code" on the micelle surface that matches the structural features of the peptide chain. Hydrophobic "dimples" are constructed on imprinted micelles that match the hydrophobic side chains of the peptide precisely in size and shape. Polar binding functionalities are installed at correct positions to interact with specific acidic and basic groups on the peptide. Secondary hydrogen-bonding and electrostatic interactions are introduced through imprinting to enhance the binding affinity and specificity further. Binding affinities of tens of nanomolar are readily achieved in water for biological peptides with over a dozen residues. Excellent binding selectivity is observed even for subtly different peptides. The synthesis of these protein-sized nanoparticles involves a one-pot reaction complete within 2 days; purification requires nothing but precipitation and solvent washing. These features make the molecularly imprinted nanoparticles (MINPs) highly promising peptide-binding "artificial antibodies" for chemical and biological applications.

Detection of ciprofloxacin through surface plasmon resonance nanosensor with specific recognition sites

The novel nanosensor based on Surface Plasmon Resonance (SPR) was developed for sensitive and selective detection of ciprofloxacin via molecularly imprinted nanoparticles (MIP/NPs). NPs were synthesized through miniemulsion polymerization technique with methacrylic acid as a functional monomer. FTIR, SEM, zetasizer and contact angle measurements were used for the characterization of MIP/NPs. After modification the SPR chip surface, the nanosensor was used for detection of ciprofloxacin in aqueous solution. According to selected concentration range, the correlation coefficient and limit of detections were obtained as 0.993 (R2) and 3.21 and 7.1 ppb in ultrapure water and SWW, respectively. Association kinetic analysis, Scatchard, Freundlich, Langmuir and Freundlich-Langmuir isotherms were also performed on the data to investigate adsorption behaviour of ciprofloxacin on the surface of nanosensor. Tetracycline and enrofloxacin were used as competitor agents to examine the selectivity of nanosensor. Performance of the SPR nanosensor was also investigated by using synthetic wastewater (SWW) for detection of CPX. The reusability of nanosensor was investigated and good repeatability was obtained with 5.81% RSD. As a result, selective, simple and low-cost method to detect ciprofloxacin in aqueous solution was developed by combining MIP/NPs and SPR.

Molecularly imprinted nanoparticles grafted to porous silica as chiral selectors in liquid chromatography

The work presented here explores the grafting of molecularly imprinted nanoparticles (MIN) on silica beads for the development of new chiral stationary phases (CSP). Both solid-phase imprinting and precipitation polymerisation were tested for MIN synthesis though the latter approach was the only one that provided efficient chiral selectors. MIN particles were prepared by iniferter polymerisation initiated by UV radiation, using itaconic acid as functional monomer and ethylene dimethacrylate as cross-linker. This resulted in particles with an average size of 249.0±4.0nm which were covalently immobilised onto chromatographic silica beads. The resultant CSP based on the composite silica beads-MIN was capable of resolving the racemate of the antidepressant drug citalopram and also separating its major metabolites by liquid chromatography, with better efficiency and peak symmetry than other MIP based CSP. The methodology presented here allowed for the quantification of the pharmacologically active enantiomer (+)-(S)-citalopram (SCIT) and its main metabolites (+)-(S)-desmethylcitalopram (SDCIT) and (+)-(S)-didesmethylcitalopram (SDDCIT) in urine, registering mean recoveries that ranged from 91.5 to 103.7% with RSD values that were below 10% in all tested concentration levels (0.1, 0.75 and 5μgmL−1), which confirmed method suitability for the intended application.

Green synthesis of water-compatible and thermo-responsive molecularly imprinted nanoparticles

Through precipitation polymerization, a novel water-compatible and positive thermo-responsive molecularly imprinted nanoparticle (MINP) was successfully synthesized in aqueous solution using acrylamide (AAm) and 2-acrylamide-2-methyl propanesulfonic acid (AMPS) as functional monomer, N,N′-methylenebis(acrylamide) (MBA) as cross-linker, and levofloxacin (LOFL) as template. The MINP was composed of LOFL imprinted matrix, which showed positively thermo-responsive interpolymer interaction between poly(AAm) and poly(AMPS). To obtain MINP with excellent molecular recognition ability, the composition and ratio of recipe were optimized in detail. The resultant MINP was characterized by transmission electron microscope, thermogravimetric analysis, nitrogen adsorption–desorption isotherms, and Fourier transform infrared spectra. The binding behavior demonstrated the zipper-like switchable molecular recognition ability for temperature. The low temperature could stabilize interpolymer interaction between poly(AAm) and poly(AMPS), thus the MINP demonstrated poor molecular recognition ability at 20°C. In contrast, the high temperature resulted to the dissociation of poly(AAm)-poly(AMPS) complexes and promote the mass transfer of target in and out the MINP. Therefore, the MINP exhibited significant molecular recognition ability at 40°C. In contrast to previously inverse thermo-responsive nanomaterials, this zipper-like thermo-responsive MINP is unique and has prospects in extensive application.

Water compatible molecularly imprinted nanoparticles as a restricted access material for extraction of hippuric acid, a biological indicator of toluene exposure, from human urine

The authors describe the preparation of molecularly imprinted nanoparticles (MINPs) for the solid phase extraction of hippuric acid (HA). The MINPs consists of a water-compatible organic-inorganic silica composite which was obtained from a functionalized silica by the sol-gel method. HA acted as the template, 3-aminopropyl trimethoxysilane as the functional monomer, and tetraethoxysilane as the crosslinker. Subsequently, methacryloxypropyltrimethoxysilane was used as a coupling agent to deposit a hydrophilic acrylamide coating onto the surface of the MINPs. The morphology and structure of the resulting restricted access material (referred to as RAM-MINP) were characterized by scanning electron microscopy, transmission electron microscopy and Fourier transform infrared spectroscopy. Solid phase extraction of HA was accomplished by passing urine samples through a RAM-MINP-packed SPE cartridge. Following elution, HA was quantified by HPLC using UV detection at 228 nm. The effects of sample pH, amount of sorbent and eluent and washing solvent volumes were optimized by experimental design methodology under response surface methodology. Under optimized conditions, the mean extraction efficiency of HA from spiked samples is adequately repeatable, with relative standard deviations of <6.1%. The limits of detection and quantitation are 0.15 and 0.25 μg.L−1, respectively.

Molecularly imprinted nanoparticles and their releasing properties, bio-distribution as drug carriers

Molecular imprinted nanoparticles (MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carriers. We synthesized MINPs via precipitation polymerization with vinblastine (VBL) as a model drug, and investigated the drug loading, releasing property in vitro and bio-distribution in vivo. The obtained MINPs, from 300 to 450 nm, had smooth surface and favorable dispersibility. The entrapment efficacy and drug loading capacity of VBL loaded MINPs (MINPs-VBL) were 83.25% and 8.72% respectively. In PBS (pH7.4), MINPs-VBL showed sustained release behavior. The cumulative release percentage reached about 70% during 216 h and no burst release was observed. The releasing behavior of MINPs-VBL in vitro conformed to the first-order kinetics model. MINPs-VBL and commercially available vinblastine sulfate injection (VBL injection) were injected via tail vein of SD rats respectively to investigate the bio-distribution. MINPs-VBL group showed higher concentration of VBL in tissues and serum than VBL injection group after 60 min, and the drug level in liver was the highest. MINPs-VBL exhibited liver targeting trend to some extent, which was based on the evaluation of drug targeting index (DTI) and drug selecting index (DSI).

Water-Soluble Molecularly Imprinted Nanoparticle Receptors with Hydrogen-Bond-Assisted Hydrophobic Binding.

Molecularly imprinted nanoparticles (MINPs) were prepared when surfactants with a tripropargylammonium headgroup and a methacrylate-functionalized hydrophobic tail were cross-linked in the micelle form on the surface and in the core in the presence of hydrophobic template molecules. With the surfactants containing an amide bond near the headgroup, the MINPs had a layer of hydrogen-bonding groups in the interior that strongly influenced their molecular recognition. Templates/guests with strong hydrogen-bonding groups in the midsection of the molecule benefited most, especially if the hydrophobe of the template could penetrate the amide layer to reach the hydrophobic core of the cross-linked micelles. The location and the orientation of the hydrophilic groups were also important, as they determined how the template interacted with the surfactant micelles and, ultimately, with the MINP receptors.

A New Versatile Water-Soluble Iniferter Platform for the Preparation of Molecularly Imprinted Nanoparticles by Photopolymerisation in Aqueous Media.

The multi-step synthesis of a new water-soluble dithiocarbamate iniferter platform for the preparation of nanoparticles and -gels in aqueous solvents by photoinduced living-radical polymerisation is described herein. The water solubility of the dithiocarbamate iniferter was achieved by incorporating two unprotected glucose units into the iniferter structure by copper(I)-catalysed azide-alkyne cycloaddition ("click chemistry"). Molecularly imprinted nanoparticles (MIPs) specific for 2,4-dichlorophenoxyacetic acid and the corresponding non-imprinted particles (NIPs) were prepared in pure water by using the prepared iniferter as photoinitiator. Radioligand binding tests confirmed a high imprinting factor, and the living character of the iniferter was demonstrated by re-initiating a second photochemical polymerisation on the NIP nanoparticles in water by using ethylene glycol methacrylate phosphate. Our newly synthesised structure is a promising tool for iniferter-mediated photopolymerisations in aqueous media for the preparation of biocompatible nanomaterials with high potential for biomedical applications in a bottom-up fashion.