Molecularly imprinted sensor based on poly-o-phenylenediamine-hydroquinone polymer for ß-amyloid-42 detection.

A sensitive and selective molecularly imprinted polymer (MIP) sensor was developed for the determination of amyloid-ß (1-42) (Aß42). The glassy carbon electrode (GCE) was successively modified with electrochemical reduction graphene oxide (ERG) and poly(thionine-methylene blue) (PTH-MB). The MIPs were synthesized by electropolymerization with Aß42 as a template and o-phenylenediamine (o-PD) and hydroquinone (HQ) as functional monomers. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), chronoamperometry (CC), and differential pulse voltammetry (DPV) were used to study the preparation process of the MIP sensor. The preparation conditions of the sensor were investigated in detail. In optimal experimental conditions, the response current of the sensor was linear in the range of 0.12-10 µg mL-1 with a detection limit of 0.018 ng mL-1. The MIP-based sensor successfully detected Aß42 in commercial fetal bovine serum (cFBS) and artificial cerebrospinal fluid (aCSF).

Molecularly Imprinted Materials for Selective Biological Recognition.

Molecular imprinting is an approach of generating imprinting cavities in polymer structures that are compatible with the target molecules. The cavities have memory for shape and chemical recognition, similar to the recognition mechanism of antigen-antibody in organisms. Their structures are also called biomimetic receptors or synthetic receptors. Owing to the excellent selectivity and unique structural predictability of molecularly imprinted materials (MIMs), practical MIMs have become a rapidly evolving research area providing key factors for understanding separation, recognition, and regenerative properties toward biological small molecules to biomacromolecules, even cell and microorganism. In this review, the characteristics, morphologies, and applicability of currently popular carrier materials for molecular imprinting, especially the fundamental role of hydrogels, porous materials, hierarchical nanoparticles, and 2D materials in the separation and recognition of biological templates are discussed. Moreover, through a series of case studies, emphasis is given on introducing imprinting strategies for biological templates with different molecular scales. In particular, the differences and connections between small molecular imprinting (bulk imprinting, "dummy" template imprinting, etc.), large molecular imprinting (surface imprinting, interfacial imprinting, etc.), and cell imprinting strategies are demonstrated in detail. Finally, future research directions are provided.

Blood-brain barrier permeable carbon nano-assemblies for amyloid-ß clearance and neurotoxic attenuation.

Abnormal amyloid ß-protein (Aß42) fibrillation is a key event in Alzheimer's disease (AD), and photodynamic therapy (PDT) possesses great potential in modulating Aß42 self-assembly. However, the poor blood-brain barrier (BBB) penetration, low biocompatibility, and limited tissue penetration depth of existing photosensitizers limit the progress of photo-oxidation strategies. In this paper, novel indocyanine green-modified graphene quantum dot nano-assemblies (NBGQDs-ICGs) were synthesized based on a molecular assembly strategy of electrostatic interactions for PDT inhibition of Aß42 self-assembly process and decomposition of preformed fibrils under near-infrared light. Combining the small-size structure of graphene quantum dots and the near-infrared light-responsive properties of ICGs, the NBGQDs-ICGs could achieve BBB penetration under 808 nm irradiation. More importantly, the neuroprotective mechanism of NBGQDs-ICG was studied for the first time by AFM, which effectively weakened the adhesion of Aß42 aggregates to the cell surface by blocking the interaction between Aß42 and the cell membrane, and restored the mechanical stability and adhesion of the neuron membrane. Meanwhile, NBGQDs-ICG promoted phagocytosis of Aß42 by microglia. In addition, the good biocompatibility and stability ensured the biosafety of NBGQDs-ICG in future clinical applications. We anticipate that such multifunctional nanocomponents may provide promising avenues for the development of novel AD inhibitors.

Photooxidative inhibition and decomposition of ß-amyloid in Alzheimer's by nano-assemblies of transferrin and indocyanine green.

Photoinduced modulation of Aß42 aggregation has emerged as a therapeutic option for treating Alzheimer's disease (AD) due to its high spatiotemporal controllability, noninvasive nature, and low systemic toxicity. However, existing photo-oxidants have the poor affinity for Aß42, low depolymerization efficiency, and difficulty in crossing the blood-brain barrier (BBB), hindering their application in the treatment of AD. Here, through hydrophobic interactions and hydrogen bonding, we integrated the near-infrared (NIR) photosensitizer indocyanine green with transferrin (denoted as TF-ICG), a protein with a high affinity for Aß42, and demonstrated its anti-amyloid activity in vitro. TF-ICG was shown to bind to Aß42 residues via hydrophobic interaction, impeding π-π stacking of Aß42 peptide monomers and disassembling mature Aß42 protofibrils in a concentration-dependent manner. More importantly, under NIR (808 nm, 0.6w/cm2) irradiation, TF-ICG completely inhibited the fibrillation process of Aß42 to generate amorphous aggregates, with an inhibition rate of 96 % at only 65 nM. Meanwhile, TF-ICG could photo-oxidize rigid Aß42 aggregates and break them down into small amorphous structures. Tyrosine fluorescence assay further demonstrated the intrinsic affinity and targeting of TF-ICG to Aß42 fibrils. In vitro studies validated the anti-amyloid activity of TF-ICG, which provided a theoretical basis for further in vivo application as a BBB-penetrating nanotherapeutic platform.

Curcumin-loaded protein imprinted mesoporous nanosphere for inhibiting amyloid aggregation.

Some natural variants of human lysozyme are associated with systemic non-neurological amyloidosis that leads to amyloid protein fibril deposition in different tissues. Inhibition of amyloid fibrillation by nanomaterials is considered to be an effective approach to treating amyloidosis. Here, we prepared a targeted, highly loaded curcumin lysozyme-imprinted nanosphere (CUR-MIMS) that could effectively inhibit the aggregation of lysozyme with lysozyme adsorption capacity of 193.57 mg g-1 and the imprinting factor (IF) of 3.72. CUR-MIMS could bind to lysozyme through hydrophobic interactions and effectively reduce the hydrophobicity of the total solvent-exposed surface in lysozyme fibrillation, thus reducing the self-assembly process triggered by hydrophobic interactions. Thioflavin T (ThT) analysis demonstrated that CUR-MIMS inhibited the aggregation of amyloid fibrils in a dose-dependent manner (inhibition efficiency of 56.07 %). Circular dichroism (CD) spectrum further illustrated that CUR-MIMS could significantly inhibit the transition of lysozyme from α-helix structure to ß-sheet. More importantly, biological experiments proved the good biocompatibility of CUR-MIMS, which indicated the potential of our system as a future therapeutic platform for amyloidosis.