Quartz Crystal Microbalance Method to Measure Nanoparticle-Receptor Interactions and Evaluate Nanoparticle Design Efficiency.

Conjugation of biomolecules on the surface of nanoparticles (NPs) to achieve active targeting is widely investigated within the scientific community. However, while a basic framework of the physicochemical processes underpinning bionanoparticle recognition is now emerging, the precise evaluation of the interactions between engineered NPs and biological targets remains underdeveloped. Here, we show how the adaptation of a method currently used to evaluate molecular ligand-receptor interactions by quartz crystal microbalance (QCM) can be used to obtain concrete insights into interactions between different NP architectures and assemblies of receptors. Using a model bionanoparticle grafted with oriented apolipoprotein E (ApoE) fragments, we examine key aspects of bionanoparticle engineering for effective interactions with target receptors. We show that the QCM technique can be used to rapidly measure construct-receptor interactions across biologically relevant exchange times. We contrast random adsorption of the ligand at the surface of the NPs, resulting in no measurable interaction with target receptors, to grafted oriented constructs, which are strongly recognized even at lower graft densities. The effects of other basic parameters impacting the interaction such as ligand graft density, receptor immobilization density, and linker length were also efficiently evaluated with this technique. Dramatic changes in interaction outcomes with subtle alterations in these parameters highlight the general importance of measuring the interactions between engineered NPs and target receptors ex situ early on in the construct development process for the rational design of bionanoparticles.

Designing Functional Bionanoconstructs for Effective In Vivo Targeting.

The progress achieved over the last three decades in the field of bioconjugation has enabled the preparation of sophisticated nanomaterial-biomolecule conjugates, referred to herein as bionanoconstructs, for a multitude of applications including biosensing, diagnostics, and therapeutics. However, the development of bionanoconstructs for the active targeting of cells and cellular compartments, both in vitro and in vivo, is challenged by the lack of understanding of the mechanisms governing nanoscale recognition. In this review, we highlight fundamental obstacles in designing a successful bionanoconstruct, considering findings in the field of bionanointeractions. We argue that the biological recognition of bionanoconstructs is modulated not only by their molecular composition but also by the collective architecture presented upon their surface, and we discuss fundamental aspects of this surface architecture that are central to successful recognition, such as the mode of biomolecule conjugation and nanomaterial passivation. We also emphasize the need for thorough characterization of engineered bionanoconstructs and highlight the significance of population heterogeneity, which too presents a significant challenge in the interpretation of in vitro and in vivo results. Consideration of such issues together will better define the arena in which bioconjugation, in the future, will deliver functional and clinically relevant bionanoconstructs.

A Nanoscale Shape-Discovery Framework Supporting Systematic Investigations of Shape-Dependent Biological Effects and Immunomodulation.

Since it is now possible to make, in a controlled fashion, an almost unlimited variety of nanostructure shapes, it is of increasing interest to understand the forms of biological control that nanoscale shape allows. However, a priori rational investigation of such a vast universe of shapes appears to present intractable fundamental and practical challenges. This has limited the useful systematic investigation of their biological interactions and the development of innovative nanoscale shape-dependent therapies. Here, we introduce a concept of biologically relevant inductive nanoscale shape discovery and evaluation that is ideally suited to, and will ultimately become, a vehicle for machine learning discovery. Combining the reproducibility and tunability of microfluidic flow nanochemistry syntheses, quantitative computational shape analysis, and iterative feedback from biological responses in vitro and in vivo, we show that these challenges can be mastered, allowing shape biology to be explored within accepted scientific and biomedical research paradigms. Early applications identify significant forms of shape-induced biological and adjuvant-like immunological control.

Metal-Organic Gels from Silver Nanoclusters with Aggregation-Induced Emission and Fluorescence-to-Phosphorescence Switching.

Luminescent metal nanoclusters (NCs) are emerging as a new class of functional materials that have rich physicochemical properties and wide potential applications. In recent years, it has been found that some metal NCs undergo aggregation-induced emission (AIE) and an interesting fluorescence-to-phosphorescence (F-P) switching in solutions. However, insights of both the AIE and the F-P switching remain largely unknown. Now, gelation of water soluble, atomically precise Ag9 NCs is achieved by the addition of antisolvent. Self-assembly of Ag9 NCs into entangled fibers was confirmed, during which AIE was observed together with an F-P switching occurring within a narrow time scale. Structural evaluation indicates the fibers are highly ordered. The self-assembly of Ag9 NCs and their photoluminescent property are thermally reversible, making the metal-organic gels good candidates for luminescent ratiometric thermometers.

Amino-Acid-Mediated Biomimetic Formation of Light-Harvesting Antenna Capable of Hydrogen Evolution.

The control of materials concerning size as well as high-order organization may have profound implications for a wide variety of technologies. Herein, we develop a facile strategy to fabricate hierarchically organized amino acid and quantum dot (QD) biomimetic light-harvesting antenna via the integration of coordination-driven self-assembly and bioinspired mineralization. Simplified from phytochelatins, cystine is used as a chelating agent to bind cadmium ions (Cd2+). This coordination interaction further drives the self-assembly of cystine into hierarchical hybrid crystals. The hybrid templates can provide ordered sites for in situ mineralization of cadmium sulfide (CdS) to generate hierarchical three-dimensional QDs architectures. Optimal light harvesting properties are obtained by controlling the mineralization conditions, which facilitates photocatalytic hydrogen (H2) evolution. In addition, the CdS QDs architectures possess sustainable photocatalytic performance because of robust assembled structures, rendering them potent candidates for optoelectronic applications.

Self-Assembled Zinc/Cystine-Based Chloroplast Mimics Capable of Photoenzymatic Reactions for Sustainable Fuel Synthesis.

Prototypes of biosystems provide good blueprints for the design and creation of biomimetic systems. However, mimicking both the sophisticated natural structures and their complex biological functions still remains a great challenge. Herein, chloroplast mimics have been fabricated by one-step bioinspired amino acid mineralization and simultaneous integration of catalytically active units. Hierarchically structured crystals were obtained by the metal-ion-directed self-assembly of cystine (the oxidized dimer of the amino acid cysteine), with a porous structure and stacks of nanorods, which show similar architectural principles to chloroplasts. Porphyrins and enzymes can both be encapsulated inside the crystal during mineralization, rendering the crystal photocatalytically and enzymatically active for an efficient and sustainable synthesis of hydrogen and acetaldehyde in a coupled photoenzymatic reaction.

Tunable Aggregation-Induced Emission of Polyoxometalates via Amino Acid-Directed Self-Assembly and Their Application in Detecting Dopamine.

In this work, through the aqueous phase self-assembly of an Eu-containing polyoxometalate (POM), Na9[EuW10O36]·32H2O (EuW10) and different amino acids, we obtained spontaneously formed vesicles that showed luminescence enhancement for EuW10 and arginine (Arg), lysine (Lys), or histidine (His) complexes, but luminescence quenching for EuW10 and glutamic acid (Glu) or aspartic acid (Asp) complexes. The binding mechanisms between them have been explored at the molecular level by using different characterization techniques. It was found that EuW10 acted as polar head groups interact with the positively charged residues for alkaline amino acids, protonated amide groups for acidic amino and nonpolar acid aminos through electrostatic interactions, and the remaining segments of amino acids served as relatively hydrophobic parts aggregated together forming bilayer membrane structures. Moreover, the different influences of amino acids on the fluorescence property of EuW10 revealed that the electrostatic interaction between the positive charged group of amino acid and the polyanionic cluster dominates the fluorescence properties of assemblies. Furthermore, a turn-off sensing application of the EuW10/Arg platform to probe dopamine (DA) against various other biological molecules such as neurotransmitters or amino acids was also established. The concept of combining POMs with amino acids extends the research category of POM-based functional materials and devices.

Fluorescent oligomer as a chemosensor for the label-free detection of Fe(3+) and dopamine with selectivity and sensitivity.

In this article, a sensitive and selective turn-off fluorescence chemosensor, Tyloxapol (one kind of water soluble oligomer), was developed for the label-free detection of Fe(3+) ions in aqueous solution. Fluorescence (FL) experiments demonstrated that Tyloxapol was a sensitive and selective fluorescence sensor for the detection of Fe(3+) directly in water over a wide range of metal cations including Na(+), K(+), Ag(+), Hg(2+), Cd(2+), Co(2+), Cu(2+), Cr(3+), Mn(2+), Ba(2+), Zn(2+), Ni(2+), Mg(2+), Ca(2+), and Pb(2+). Moreover, the fluorescence intensity of Tyloxapol has shown a linear response to Fe(3+) in the concentration range of 0-100 µmol L(-1) with a detection limit of 2.2 µmol L(-1) in aqueous solution. Next, based on a competition mechanism, another turn-on sensing application of the Tyloxapol/Fe(3+) platform to probe dopamine (DA) against various other biological molecules such as other neurotransmitters or amino acids (norepinephrine bitartrate, acetylcholine chloride, alanine, valine, phenylalanine, tyrosine, leucine, glycine, histidine) were also investigated. It is expected that our strategy may offer a new approach for developing simple, cost-effective, rapid and sensitive sensors in biological and environmental applications.