This Review presents polysaccharides, oligosaccharides, nucleic acids, peptides, and proteins as functional stimuli-responsive polymer scaffolds that yield hydrogels with controlled stiffness. Different physical or chemical triggers can be used to structurally reconfigure the crosslinking units and control the stiffness of the hydrogels. The integration of stimuli-responsive supramolecular complexes and stimuli-responsive biomolecular units as crosslinkers leads to hybrid hydrogels undergoing reversible triggered transitions across different stiffness states. Different applications of stimuli-responsive biomolecule-based hydrogels are discussed. The assembly of stimuli-responsive biomolecule-based hydrogel films on surfaces and their applications are discussed. The coating of drug-loaded nanoparticles with stimuli-responsive hydrogels for controlled drug release is also presented.

Stimuli-Responsive Biomolecule-Based Hydrogels and Their Applications

Self-assembly is the process of association of individual units of a material into highly arranged/ordered structures/patterns. It imparts unique properties to both inorganic and organic structures, so generated, via non-covalent interactions. Currently, self-assembled nanomaterials are finding a wide variety of applications in the area of nanotechnology, imaging techniques, biosensors, biomedical sciences, etc., due to its simplicity, spontaneity, scalability, versatility, and inexpensiveness. Self-assembly of amphiphiles into nanostructures (micelles, vesicles, and hydrogels) happens due to various physical interactions. Recent advancements in the area of drug delivery have opened up newer avenues to develop novel drug delivery systems (DDSs) and self-assembled nanostructures have shown their tremendous potential to be used as facile and efficient materials for this purpose. The main objective of the projected review is to provide readers a concise and straightforward knowledge of basic concepts of supramolecular self-assembly process and how these highly functionalized and efficient nanomaterials can be useful in biomedical applications. Approaches for the self-assembly have been discussed for the fabrication of nanostructures. Advantages and limitations of these systems along with the parameters that are to be taken into consideration while designing a therapeutic delivery vehicle have also been outlined. In this review, various macro- and small-molecule-based systems have been elaborated. Besides, a section on DNA nanostructures as intelligent materials for future applications is also included.

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Nanoscale Self-Assembly for Therapeutic Delivery.

For the development of advanced flexible and wearable electronic devices, functional electrolytes with excellent conductivity, temperature tolerance, and desirable mechanical properties need to be engineered. Herein, an alkaline double-network hydrogel with high conductivity and superior mechanical and antifreezing properties is designed and promisingly utilized as the flexible electrolyte in all-solid-state zinc-air batteries. The conductive hydrogel is comprised of covalently cross-linked polyelectrolyte poly(2-acrylamido-2-methylpropanesulfonic acid potassium salt) (PAMPS-K) and interpenetrating methyl cellulose (MC) in the presence of concentrated alkaline solutions. The covalently cross-linked PAMPS-K skeleton and interpenetrating MC chains endow the hydrogel with good mechanical strength, toughness, an extremely rapid self-recovery capability, and an outstanding antifatigue property. Gratifyingly, the entrapment of a concentrated alkaline solution in the hydrogel matrix yields an extremely high ionic conductivity (105 mS cm-1 at 25 °C) and an excellent antifreezing capacity. The hydrogel retains comparable conductivity and eligible strength to withstand various mechanical deformations at -20 °C. The all-solid-state zinc-air batteries using PAMPS-K/MC hydrogels as flexible alkaline electrolytes exhibit comparable values of specific capacity (764.7 mAh g-1), energy capacity (850.2 mWh g-1), cycling stability, and mechanical flexibility. The batteries still possess competitive electrochemical performances even when the operating temperature drops to -20 °C.

Alkaline Double-Network Hydrogels with High Conductivities, Superior Mechanical Performances, and Antifreezing Properties for Solid-State Zinc–Air Batteries

Self-assembled natural phytochemicals for synergistically antibacterial application from the enlightenment of traditional Chinese medicine combination

Compounds with a nitrobenzoxadiazole (NBD) skeleton exhibit prominent useful properties including environmental sensitivity, high reactivity toward amines and biothiols (including H2S) accompanied by distinct colorimetric and fluorescent changes, fluorescence-quenching ability, and small size, all of which facilitate biomolecular sensing and self-assembly. Amines are important biological nucleophiles, and the unique activity of NBD ethers with amines has allowed for site-specific protein labelling and for the detection of enzyme activities. Both H2S and biothiols are involved in a wide range of physiological processes in mammals, and misregulation of these small molecules is associated with numerous diseases including cancers. In this review, we focus on NBD-based synthetic probes as advanced chemical tools for biomolecular sensing. Specifically, we discuss the sensing mechanisms and selectivity of the probes, the design strategies for multi-reactable multi-quenching probes, and the associated biological applications of these important constructs. We also highlight self-assembled NBD-based probes and outline future directions for NBD-based chemosensors. We hope that this comprehensive review will facilitate the development of future probes for investigating and understanding different biological processes and aid the development of potential theranostic agents.

NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.

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Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

/pdf/author-correction-directed-self-assembly-of-herbal-small-1893bhlucj.pdf

Author Correction: Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation

Numerous intra- and inter-chromosomal contacts have been mapped in eukaryotic genomes, but it remains challenging to link these 3D structures to their regulatory functions. To establish the causal relationships between chromosome conformation and genome functions, we develop a method, Chemically Induced Chromosomal Interaction (CICI), to selectively perturb the chromosome conformation at targeted loci. Using this method, long-distance chromosomal interactions can be induced dynamically between intra- or inter-chromosomal loci pairs, including the ones with very low Hi-C contact frequencies. Measurement of CICI formation time allows us to probe chromosome encounter dynamics between different loci pairs across the cell cycle. We also conduct two functional tests of CICI. We perturb the chromosome conformation near a DNA double-strand break and observe altered donor preference in homologous recombination; we force interactions between early and late-firing DNA replication origins and find no significant changes in replication timing. These results suggest that chromosome conformation plays a deterministic role in homology-directed DNA repair, but not in the establishment of replication timing. Overall, our study demonstrates that CICI is a powerful tool to study chromosome dynamics and 3D genome function. 

https://www.nature.com/articles/s41467-022-28416-3.pdf

Yujie Yan

Papers

Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation

Author Correction: Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation

Chemically Induced Chromosomal Interaction (CICI) method to study chromosome dynamics and its biological roles