Blood cellular membrane-coated Au/polydopamine nanoparticle-targeted NIR-II antibacterial therapy.

Bacterial infections are the primary causes of infectious diseases in humans. In recent years, the abuse of antibiotics has led to the widespread enhancement of bacterial resistance. Concerns have been raised about the identification of a common treatment platform for bacterial infections. In this study, a composite nanomaterial was used for near-infrared II (NIR-II) photothermal antibacterial treatment. Red blood cell membrane was peeled and coated onto the surface of the Au/polydopamine nanoparticle-containing aptamer. The composite nanomaterials based on Au/polydopamine exhibit highest photothermal conversion capability. Moreover, these assembled nanoparticles can quickly enter the body's circular system with a specific capability to recognise bacteria. In vivo experiments demonstrated that the composites could kill bacteria from infected blood while significantly reducing the level of bacteria in various organs. Such assemblies offer a paradigm for the treatment of bacterial infections caused by the side effects of antibiotics.

Ion-Induced Nanoarchitectonics for Anthraquinone Single Crystals with Enhanced Fluorescence Properties.

Recently, bioinspired fluorescent materials have drawn ever-increasing attention due to their ecofriendliness and easy accessibility. Herein, we demonstrate that anthraquinone/metal ion coordination complexes can form well-defined crystals and possess obvious fluorescence enhancement properties. The fluorescence quantum yields of anthraquinone/metal ion assemblies are more than 2 orders of magnitude compared to those of anthraquinone assemblies. The electronic structures of the first excited singlet states of anthraquinone/metal ion molecules are obtained, and the mechanism of the fluorescence enhancement is elucidated. Such photoluminescent anthraquinone/metal ion crystals can be considered as efficient phosphors in fabricating light-emitting diodes. This work provides a simple route for the development of highly efficient natural fluorescent materials.

Nanoarchitectonics with a Membrane-Embedded Electron Shuttle Mimics the Bioenergy Anabolism of Mitochondria.

Enhanced bioenergy anabolism through transmembrane redox reactions in artificial systems remains a great challenge. Here, we explore synthetic electron shuttle to activate transmembrane chemo-enzymatic cascade reactions in a mitochondria-like nanoarchitecture for augmenting bioenergy anabolism. In this nanoarchitecture, a dendritic mesoporous silica microparticle as inner compartment possesses higher load capacity of NADH as proton source and allows faster mass transfer. In addition, the outer compartment ATP synthase-reconstituted proteoliposomes. Like natural enzymes in the mitochondrion respiratory chain, a small synthetic electron shuttle embedded in the lipid bilayer facilely mediates transmembrane redox reactions to convert NADH into NAD+ and a proton. These facilitate an enhanced outward proton gradient to drive ATP synthase to rotate for catalytic ATP synthesis with improved performance in a sustainable manner. This work opens a new avenue to achieve enhanced bioenergy anabolism by utilizing a synthetic electron shuttle and tuning inner nanostructures, holding great promise in wide-range ATP-powered bioapplications.

Tunable Chirality of Self-Assembled Dipeptides Mediated by Bipyridine Derivative.

Supramolecular peptide assemblies have been widely used for the development of biomedical, catalytical, and optical materials with chiral nanostructures in view of the intrinsic chirality of peptides. However, the assembly pathway and chiral transformation behavior of various peptides remain largely elusive especially for the transient assemblies under out-of-equilibrium conditions. Herein, the N-fluorenylmethoxycarbonyl-protected phenylalanine-tyrosine dipeptide (Fmoc-FY) was used as a peptide assembly platform, which showed that the assembly proceeds multistep evolution. The original spheres caused by liquid-liquid phase separation (LLPS) can nucleate and elongate into the formation of right-handed helices which were metastable and easily converted into microribbons. Interestingly, a bipyridine derivative can be introduced to effectively control the assembly pathway and induce the formation of thermodynamically stable right-handed or left-handed helices at different stoichiometric ratios. In addition, the chiral assembly can also be regulated by ultrasound or enzyme catalysis. This minimalistic system not only broadens the nucleation-elongation mechanisms of protein aggregates but also promotes the controllable design and development of chiral biomaterials.

Photozyme-Catalyzed ATP Generation Based on ATP Synthase-Reconstituted Nanoarchitectonics.

We demonstrate that ATP synthase-reconstituted proteoliposome coatings on the surface of microcapsules can realize photozyme-catalyzed oxidative phosphorylation. The microcapsules were assembled through layer-by-layer deposition of semiconducting graphitic carbon nitride (g-C3N4) nanosheets and polyelectrolytes. It is found that electrons from polyelectrolytes are transferred to g-C3N4 nanosheets, which enhances the separation of photogenerated electron-hole pairs. Thus, the encapsulated g-C3N4 nanosheets as the photozyme accelerate oxidation of glucose into gluconic acid to yield protons under light illumination. The outward transmembrane proton gradient is established to drive ATP synthase to synthesize adenosine triphosphate. With such an assembled system, light-driven oxidative phosphorylation is achieved. This indicates that an assembled photozyme can be used for oxidative phosphorylation, which creates an unusual way for chemical-to-biological energy conversion. Compared to conventional oxidative phosphorylation systems, such an artificial design enables higher energy conversion efficiency.

Emodin-Based Nanoarchitectonics with Giant Two-Photon Absorption for Enhanced Photodynamic Therapy.

Two-photon-excited photodynamic therapy (TPE-PDT) has significant advantages over conventional photodynamic therapy (PDT). However, obtaining easily accessible TPE photosensitizers (PSs) with high efficiency remains a challenge. Herein, we demonstrate that emodin (Emo), a natural anthraquinone (NA) derivative, is a promising TPE PS with a large two-photon absorption cross-section (TPAC: 380.9 GM) and high singlet oxygen (1 O2 ) quantum yield (31.9 %). When co-assembled with human serum albumin (HSA), the formed Emo/HSA nanoparticles (E/H NPs) possess a giant TPAC (4.02×107  GM) and desirable 1 O2 generation capability, thus showing outstanding TPE-PDT properties against cancer cells. In vivo experiments reveal that E/H NPs exhibit improved retention time in tumors and can ablate tumors at an ultra-low dosage (0.2 mg/kg) under an 800 nm femtosecond pulsed laser irradiation. This work is beneficial for the use of natural extracts NAs for high-efficiency TPE-PDT.

Functional chromopeptide nanoarchitectonics: molecular design, self-assembly and biological applications.

Chromoproteins are a class of delicate natural compounds that elegantly complex photosensitive species with proteins and play a central role in important life processes, such as photosynthesis. Inspired by chromoproteins, researchers integrate simple peptides and photosensitive molecular motifs to generate chromopeptides. Compared with chromoproteins, chromopeptides exhibit a relatively simple molecular structure, flexible and adjustable photophysical properties, and a capability of programmable self-assembly. Chromopeptide self-assembly has attracted great attention as the resultant high-level architectures exhibit an ingenious combination of photofunctions and biofunctions. This review systematically summarizes recent advances in chromopeptide nanoarchitectonics with particular focus on the design strategy, assembly mechanism, and structure-function relationship. Among them, the effect of peptide sequences and the variation in photophysical performance are critically emphasized. On this basis, various applications, including biomedicine and artificial photosynthesis, are discussed together with the future prospects of chromopeptide nanoarchitectonics. This review will provide insights into chromopeptide nanoarchitectonics and corresponding materials with precise designs, flexible nanostructures and versatile functions. In addition, knowledge involving chromopeptide nanoarchitectonics may aid in the development of many other kinds of supramolecular biological materials and bioengineering techniques.

The power of super-resolution microscopy in modern biomedical science.

Super-resolution microscopy (SRM) technology that breaks the diffraction limit has revolutionized the field of cell biology since its appearance, which enables researchers to visualize cellular structures with nanometric resolution, multiple colors and single-molecule sensitivity. With the flourishing development of hardware and the availability of novel fluorescent probes, the impact of SRM has already gone beyond cell biology and extended to nanomedicine, material science and nanotechnology, and remarkably boosted important breakthroughs in these fields. In this review, we will mainly highlight the power of SRM in modern biomedical science, discussing how these SRM techniques revolutionize the way we understand cell structures, biomaterials assembly and how assembled biomaterials interact with cellular organelles, and finally their promotion to the clinical pre-diagnosis. Moreover, we also provide an outlook on the current technical challenges and future improvement direction of SRM. We hope this review can provide useful information, inspire new ideas and propel the development both from the perspective of SRM techniques and from the perspective of SRM's applications.

Long afterglow particle enables spectral and temporal light management to boost photosynthetic efficiency.

Herein, we develop a strategy of matched spectral and temporal light management to improve photosynthetic efficiency by co-assembling natural thylakoid membrane (TM) with artificial long afterglow particle (LAP). To be specific, LAP with excellent stability and biocompatibility possesses the capabilities of light conversion and storage, optically-matched with the absorption of TM. These favorable features permit LAP as an additional well-functioned light source of photosynthesis performed by TM. As a consequence, enhanced photosynthesis is achieved after co-assembly, compared with pure TM. Under light, the rates of electron transfer, oxygen yield and adenosine triphosphate (ATP) production in this biohybrid architecture are boosted owing to down-conversion fluorescence emission from LAP. Under dark, persistent phosphorescence emission in charged LAP facilitates continual photosynthesis of TM, while that of pure TM almost stops immediately. This proof-of-concept work opens a new route to augment the photosynthetic efficiency of green plants by utilizing precise light-managed materials.

Three-dimensional (3D) bioprinting of medium toughened dipeptide hydrogel scaffolds with Hofmeister effect.

Short peptide self-assembled hydrogels as 3D bioprinting inks show excellent biocompatibility and diverse functional expansion, and have broad application prospects in cell culture and tissue engineering. However, the preparation of biological hydrogel inks with adjustable mechanical strength and controllable degradation for 3D bioprinting still faces big challenges. Herein, we develop dipeptide bio-inks that can be gelled in-situ based on Hofmeister sequence, and prepare hydrogel scaffold by using a layer-by-layer 3D printing strategy. Excitingly, after the introduction of Dulbecco's Modified Eagle's medium (DMEM), which is necessary for cell culture, the hydrogel scaffolds show an excellent toughening effect, which matches the needs of cell culture. It's notable that in the whole process of preparation and 3D printing of hydrogel scaffolds, no cross-linking agent, ultraviolet (UV), heating or other exogenous factors are involved, ensuring high biosafety and biocompatibility. After two weeks of 3D culture, millimeter-sized cell spheres are obtained. This work provides an opportunity for the development of short peptide hydrogel bioinks without exogenous factors in 3D printing, tissue engineering, tumor simulant reconstruction and other biomedical fields.

Covalently triggered self-assembly of peptide-based nanodrugs for cancer theranostics.

Covalently triggered peptide self-assembly is achieved through sequential integration of spontaneous covalent reaction and noncovalent interactions, thus both enhancing the physiological stability and extending unexpected functionality of the resulting peptide-based assemblies, different from popular supramolecular peptide self-assembly merely associated with noncovalent interactions. This review summarizes the recent progress on the development of covalently triggered peptide self-assembly for cancer theranostics. Especially, we propose the fundamental design principle of covalently triggered peptide self-assembly for constructing a variety of peptide-based assemblies including nanoparticles, nanofibers, hollow nanospheres, and other nanoarchitectures. Subsequently, the discussion is anchored in an overview of representative covalently assembled peptide-based nanodrugs for the cancer theranostics. Finally, the challenges and perspectives on the clinical potential of the covalently assembled peptide-based nanodrugs are highlighted. This review will provide new insights into construction of peptide-based nanodrugs through combination of covalent reaction and noncovalent self-assembly and prompt their clinical applications in cancer diagnosis and therapeutics.

Self-assembling nanoarchitectonics of size-controllable celastrol nanoparticles for efficient cancer chemotherapy with reduced systemic toxicity.

Celastrol, extracted from Tripterygium wilfordii Hook F, is one of the most promising natural extract for cancer treatment. Nevertheless, insufficient tumor retention and severe systemic toxicity still hinder its application. Herein, we report for the first time that Celastrol can directly self-assemble into size-controllable nanoparticles through the anti-solvent method by using different good solvent or by the variation of Celastrol concentrations. In vitro anti-cancer experiment revealed that the as-prepared nanoparticles can kill MCF-7 cells more effectively. Moreover, the nanoparticles can efficiently accumulate in tumors of the tumor bearing mice after tail vein injection. Under the administration of lethal dosage of Celastrol, the tumors are greatly suppressed and the mice maintain the activity. These results demonstrate that anti-solvent method may be a promising strategy to fabricate Celastrol nano-drugs with controllable size and less systemic toxicity for further clinical cancer treatment.

Schiff base nanoarchitectonics for supramolecular assembly of dipeptide as drug carriers.

Development of peptide-based supramolecular materials with hierarchical morphology and tunable guest loading displays broad potential as drug carrier in view of biocompatibility and biodegradability. Herein, we report a facile Schiff base nanoarchitectonic for supramolecular assembly of diphenylalanine (FF) metastable gel. The addition of trace glutaraldehyde (GA)/H2O solution induces the Schiff base reaction between GA and FF accompanying by phase transition from gel to solution. FF nanoparticles and hierarchical beaded nanofibers with autofluorescence properties can be constructed by regulating the competitive assembly between FF-H2O and FF-GA oligomer. Moreover, various guest molecules with different hydrophilic and hydrophobic properties can be easily loaded into such assembled particles and its release can be triggered under weak alkaline conditions, which show the potential application of the assembled FF system as drug carriers.

CO2 Induces Symmetry Breaking in Layered Dipeptide Crystals.

Control of symmetry breaking of materials provides large opportunities to regulate their properties and functions. Herein, we report breaking the symmetry of layered dipeptide crystals by utilizing CO2 to induce the adjacent monomolecular layers to stack from the opposite to the same direction. The role of CO2 is to cover the interlayer interaction sites and force the dipeptides to adsorb at asymmetric positions. Further, the dipeptide crystals exhibit far superior piezoelectricity after symmetry breaking and the piezoelectric voltage generated from the dipeptide-based generators becomes more than 500 % higher than before. This work reveals a potential route to engineer structures and properties of layered materials and provides a deep insight into the control of non-covalent interactions.

Super Light-Sensitive Photosensitizer Nanoparticles for Improved Photodynamic Therapy against Solid Tumors.

Photodynamic therapy (PDT) is an effective method for superficial cancer treatment. However, the limited light intensity in tissues, tumor hypoxia, and the low accumulation efficiency of photosensitizers (PSs) in tumors are still major challenges. Herein, we introduce super light-sensitive PS nanoparticles (designated HR NPs) that can increase singlet oxygen (1 O2 ) production and improve PS accumulation in tumors. HR NPs have the ability to produce a large amount of 1 O2 under ultralow power density light (0.05 mW cm-2 ) irradiation. More significantly, HR NPs have a long circulating time in tumor-bearing mice and can accumulate in tumors with high efficiency. When irradiated by light with a suitable wavelength, the nanoparticles exhibit excellent antitumor efficacy. This work will make it possible to cure solid tumors by PDT by enhancing the therapeutic effects.

Cu-boosted one-pot nanoarchitectonics for synthesis of polydopamine membranes as reusable laccase mimic.

As a good alternative for natural enzyme, enzyme mimics with artificial functional materials have attracted considerable attention. However, it remains a great challenge to develop a facile method to design laccase mimic with high catalytic activity, long-term stability and reusability. In this report, we propose the one-pot synthesis of reusable paper filter templated Cu-doped polydopamine membranes (PF@PDA/Cu) with laccase-like activity. Compared with the natural laccase, the PF@PDA/Cu membrane exhibits enhanced catalytic activity for the chemical conversion of hydroquinone into benzoquinone. Interestingly, these membranes present good tolerance to high temperature and the catalytic activity increases with the increase of temperature. Moreover, these membranes could be stored for 7 days and recycled for 5 times with negligible loss of catalytic activity. This work provides a promising paradigm for rational design and practical applications of metal-loading PDA materials based on one-pot synthesis methodology.

Microfabrication of peptide self-assemblies: inspired by nature towards applications.

Peptide self-assemblies show intriguing and tunable physicochemical properties, and thus have been attracting increasing interest over the last two decades. However, the micro/nano-scale dimensions of the self-assemblies severely restrict their extensive applications. Inspired by nature, to genuinely realize the practical utilization of the bio-organic super-architectures, it is beneficial to further organize the peptide self-assemblies to integrate the properties of the individual supermolecules and fabricate higher-level organizations for smart functional devices. Therefore, cumulative studies have been reported on peptide microfabrication giving rise to diverse properties. This review summarizes the recent development of the microfabrication of peptide self-assemblies, discussing each methodology along with the diverse properties and practical applications of the engineered peptide large-scale, highly-ordered organizations. Finally, the current limitations of the state-of-the-art microfabrication strategies are critically assessed and alternative solutions are suggested.

Schiff Base Mediated Dipeptide Assembly toward Nanoarchitectonics.

Dynamic covalent chemistry (DCC) is fascinating because of its dual nature. It perfectly combines the reversible nature of noncovalent bonds with the robustness of covalent bonds, effectively enhancing the stability of assemblies and meanwhile giving rise to unprecedented properties. Therefore, integration of DCC with supramolecular chemistry has emerged as a versatile and an extraordinarily useful approach in directing peptide assembly. This Minireview focuses on a recent strategy, which exploits dynamic Schiff base chemistry in combination with supramolecular chemistry, to mediate dipeptide assembly toward nanoarchitectonics. Diversified structures, new emergent properties, and their related applications are highlighted. Lastly, the opportunities and prospects in this exciting field are also introduced.

Controlled-Alignment Patterns of Dipeptide Micro- and Nanofibers.

Ordered assemblies of the peptide diphenylalanine (FF) are produced and deposited on planar substrates. The FF aggregate growth is achieved through precipitation from aqueous ammonia solutions induced by solvent evaporation. The applied dip-coating technique confines the FF assembly growth to a narrow zone near the three-phase contact. The growth was observed online by optical microscopy and was investigated systematically as a function of the process parameters. Depending on the external gas flow (to influence solvent evaporation), the withdrawal speed, the initial FF, and the initial ammonia concentrations, FF forms long, straight, and rigid microfibers and/or shorter, curved nanofibers. Under certain process conditions, the FF fibers can also aggregate into stripes. These can be deposited as large arrays of uniform stripes with regular widths and spacings. Scenarios leading to the various types of fibers and the stripe formation are presented and discussed in view of the experimental findings.

Flexible Recyclable Cellulose Paper Templated Cu-Doped Polydopamine Membranes with Dual Enzyme-Like Activity.

The development of high-efficiency enzyme mimics is of great significance in the field of biocatalysis. However, it remains challenging to design novel enzyme mimics with multiple enzyme-like activities, excellent stability, and good reusability. Herein, a facile molecular assembly strategy to construct dialdehyde cellulose (DAC) templated Cu-doped polydopamine (DAC@PDA/Cu) membrane with dual enzyme-like activities is presented. The Schiff base bonds formed between polydopamine (PDA) and DAC can not only accelerate the adhesion of PDA thin layer but also contribute to Cu-loading and high stability of DAC@PDA/Cu membrane. Importantly, the assembled DAC@PDA/Cu membrane exhibits a remarkable catalytic activity that is superior to the natural laccase along with high stability and excellent reusability. Moreover, the DAC@PDA/Cu membrane also demonstrates peroxidase-like activity, and it is successfully applied in the sensitive detection of ascorbic acid (AA). This work will provide a new paradigm methodology for rational design and practical applications of enzyme mimics based on bioinspired molecular assemblies.