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Hypothesis Crystalline self-assemblies of diphenylalanine (FF) are since long back considered to be related to Alzheimer's disease. An improved understanding of the mechanism behind the formation of such structures can lead to strategies for investigating the dynamic processes of assembly and disassembly of FF. Experiment The assembly, disassembly and reassembly of FF crystals are influenced by the solvent composition and can be triggered by evaporation of solvent. In this work these processes are directly monitored, and the structures obtained are analyzed. Findings The role of the solvent for assembly, disassembly and reassembly of diphenylalanine crystals has been demonstrated. The initial crystal structure formed via self-assembly of FF monomers can be transformed into needle-like crystals and further to hollow hexagonal microtubes through evaporation of the solvent. It is shown that all the assembly-disassembly processes are spontaneous and driven by thermodynamics. It is also found that some of the crystalline structures exhibit optical waveguiding properties.

A novel peptide nanodrug composed of three functional motifs, bis(pyrene), FFVLK and CREKA, was used as a two-photon excited photosensitizer for precise photodynamic therapy (PDT). The system presented excellent two-photon imaging ability, tumor target effect and high reactive oxygen species productivity for improving treatment precision and efficiency in PDT.

As low‐molecular‐weight hydrogelators, dipeptide hydrogel materials are suited for embedding multiple organic molecules and inorganic nanoparticles. Herein, a simple but precisely controllable method is presented that enables the fabrication of dipeptide‐based hydrogels by supramolecular assembly inside microfluidic channels. Water‐soluble quantum dots (QDs) as well as premixed porphyrins and a dipeptide in dimethyl sulfoxide (DMSO) were injected into a Y‐shaped microfluidic junction. At the DMSO/water interface, the confined fabrication of a dipeptide‐based hydrogel was initiated. Thereafter, the as‐formed hydrogel flowed along a meandering microchannel in a continuous fashion, gradually completing gelation and QD entrapment. In contrast to hydrogelation in conventional test tubes, microfluidically controlled hydrogelation led to a tailored dipeptide hydrogel regarding material morphology and nanoparticle distribution., A dipeptide hydrogel was obtained by dynamic assembly in the confined space of continuous‐flow microfluidics. Organic porphyrins and inorganic quantum dots (QDs) were integrated in the system for energy transfer, and dynamic structural control over hydrogel formation and QD integration occurred within the microchannel network (see picture).

Significant strides toward producing biochemical fuels have been achieved by mimicking natural oxidative and photosynthetic phosphorylation. Here, different from these strategies, we explore boric acid as a fuel for tuneable synthesis of energy-storing molecules in a cell-like supramolecular architecture. Specifically, a proton locked in boric acid is released in a modulated fashion by the choice of polyols. As a consequence, controlled proton gradients across the lipid membrane are established to drive ATP synthase embedded in the biomimetic architecture, which facilitates tuneable ATP production. This strategy paves a unique route to achieve highly efficient bioenergy conversion, holding broad applications in synthesis and devices that require biochemical fuels.

The dynamic Schiff base bond is exploited to construct monodisperse dopamine-based nanoparticles with autofluorescence and pH-sensitivity. This allows facile monitoring and pH-responsive drug release in the acidic tumor microenvironment. Anticancer drugs doxorubicin and a photosensitizer chlorin e6 are further loaded into the nanoparticles and synergistic anticancer efficacy is achieved.

It is commonly considered that amyloid-β (Aβ) fibrils are heavily involved in the neurological diseases. Establishing an external model based on the core recognition motif (diphenylalanine, FF) of Aβ would be of significance in understanding the assembly and disassembly of Aβ fibrils in living system. Herein, supramolecular gels with structure transition from amyloid-like β-sheet to different supramolecular helices were obtained through the co-assembly of a N-fluorenylmethoxycarbonyl-protected L-FF (L-FmocFF) with achiral pyridine derivatives. It is found that the different stacking modes (H- or J-aggregates) of additives and the microenvironment of chiral carbon play vital roles for the selectively chiral transfer or amplification of L-FmocFF. The dynamic process of helix formation was also captured. This work provides a convenient co-assembly way to explore the structure basis of Aβ fibrils with a controlled chirality.

Achieving synthetic architectures with simple structures and robust biomimetic catalytic activities remains a great challenge. Herein, we explore a facile supramolecular assembly approach to construct a dipeptide-based hierarchical nanoarchitecture with enhanced enzyme-like catalytic activity. In this nanoarchitecture, nanospheres are put in a chain-like arrangement through coordination-driven directional self-assembly. The reversible transformation of anisotropic nanochains to isotropic nanospheres switches biomimetic activity. Notably, the assembled nanoarchitecture exhibits a high enzyme-like activity and remarkable long-term stability to promote hydroquinone oxidation, superior to the natural counterpart. This work will pave the way to develop reversible and reusable supramolecular biocatalysts with ordered hierarchical structures for accelerating chemical transformations.

Constructing supramolecular materials with tunable properties and functions is a great challenge due to the complex competition between multiple assembly pathways. Herein, we report that dipeptides can self-assemble into aerogels with entirely different surface wettability through precisely controlling the assembly pathways. Charged groups or aromatic residues are selectively exposed on the surface of their nanoscale building blocks which results either in a superhydrophilic or highly hydrophobic surface. With this special property, single component dipeptide aerogels can play diverse roles in medical care applications. This study suggests great promise in the synthesis of supramolecular materials with different targeted functions from the same molecular unit.

A core-shell composite consisting of polypyrrole (PPy) coating on Au nanorods with high two-photon photothermal efficiency and good photostability have been fabricated via a facile interfacial polymerization. Transmission electron microscopy confirmed the core-shell structure of the uniform Au-PPy nanorods. The core-shell composites exhibited improved temperature elevation and photostability compared to pure Au nanorods. The composites internalized by cancer cells can be detected by strong two-photon fluorescence, thus minimizing photothermal damage to normal tissues. The cell cytotoxicity and two-photon efficiency experiments in vitro demonstrate that the composites of Au-PPy nanorods have high efficiency to inhibit the proliferation of tumor cells.

Layer-by-layer assembled TRAIL/ALG shells have been successfully coated on the surface of highly loaded doxorubicin (DOX) calcium carbonate (CaCO

Inspired by the self-assembly phenomena in nature, the instructed self-assembly of exogenous small molecules in a biological environment has become a prevalent process to control cell fate. Despite mounting examples of versatile bioactivities, the underlying mechanism remains less understood, which is in large hindered by the difficulties in the identification of those dynamic assemblies

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. G protein coupled receptor (GPER), the key player in the intercellular signaling communication, has been verified to participate in tumorigenesis. The present study aims to explore the effects of GPER on cell proliferation, invasion and EMT through CD151/miR-199a-3p bio-axis in TNBC cells. Methods: Total proteins were isolated from TNBC cell lines and GPER expression was determined using western blot assay. CCK-8 assay was used to detect cell viability after being treated with GPER activation. Western blotting and immunofluorescence were applied to measure the level of proteins associated with cell proliferation, angiogenesis and EMT, as well as the Hippo signal pathway. The level of miR-199a-3p and transfection efficiency were evaluated by reverse transcriptase quantitative PCR (RT-qPCR) after being transfected with miR-199a-3p mimics. Cell migration and invasion of TNBC cells were assessed by wound healing and transwell assays. Moreover, luciferase reporter assay was conducted to verify the relationship between CD151 and miR-199a-3p. Results: GPER activation treatment suppressed MDA-MB-231 cell viability, proliferation, migration, invasion, angiogenesis and EMT process. The expression of E-cadherin was increased, but N-cadherin, Vimentin, VEGFA, AngII and CD151 were decreased after GPER activation treatment. Conversely, inhibition of GPER indeed up-regulated CD151 expression. In addition, overexpression of miR-199a-3p supressed cell proliferation, migration, invasion and angiogenesis, as well as EMT process and the Hippo signal pathway. Conclusion: Collectively, the activation of GPER inhibits cells proliferation, invasion and EMT of triple-negative breast cancer via CD151/miR-199a-3p bio-axis. This study provides a novel intervention target for the treatment of breast cancer cells and a fresh idea for the clinical therapy of breast cancer.

Conformational transition of proteins and peptides into highly stable, β-sheet-rich structures is observed in many amyloid-associated neurodegenerative disorders, yet the precise mechanism of amyloid formation at the molecular level remains poorly understood due to the complex molecular structures. Short peptides provide simplified models for studying the molecular basis of the assembly mechanism that governs β-sheet fibrillation processes underlying the formation and inhibition of amyloid-like structures. Herein, we report a supramolecular coassembly strategy for the inhibition and transformation of stable β-sheet-rich amyloid-derived dipeptide self-assemblies into adaptable secondary structural fibrillar assemblies by mixing with bipyridine derivatives. The interplay between the type and mixing ratio of bipyridine derivatives allowed the variable coassembly process with stimuli-responsive functional properties, studied by various experimental characterizations and computational methods. Furthermore, the resulting coassemblies showed functional redox- and photoresponsive properties, making them promising candidates for controllable drug release and fluorescent imprint. This work presents a coassembly strategy not only to explore the mechanism of amyloid-like structure formation and inhibition at the molecular level but also to manipulate amyloid-like structures into responsive supramolecular coassemblies for material science and biotechnology applications.

Molecular stacking modes, generally classified as H-, J-, and X-aggregation play a key role in determining the optoelectronic properties of organic crystals. However, the control of stacking transitions of a specific molecule is an unmet challenge and a priori prediction of performance in different stacking modes is currently not possible. Herein, unexpected stacking transition from H- to J- and X- aggregation is observed in the crystal structure of a minimalistic aromatic molecule, 4,4’-bipyridine, upon co-assembled with N-acetyl-L-alanine, a non-aromatic amino acid derivative. This stacking transition improves the physicochemical properties of the co-crystals, including a large red-shifted emission, enhanced chirality, improved thermal stability and mechanical properties. While the single crystal of 4,4’-Bpy shows good optical waveguiding and piezoelectric properties, the co-crystal has a significantly lower band-gap and improved conductivity. This demonstrates the first example of H- to J- and X- packing transition of a minimalistic model by co-crystal aggregation and provides a proof-of-concept strategy for organic optoelectronics design.

In recent years, one of main obstacles in a photodynamic therapy (PDT) process has been that most photosensitizers for PDT are excited by visible light with limited penetrating ability; thus most applications of PDT are for superficial treatments. One of the methods to increase the treatment depth is to introduce a two-photon-active technique into PDT, known as TP-PDT. The difficulty here is to obtain photosensitizers with a large enough two-photon absorption cross-section. In this work, an organic nanocomplex, composed of the two-photon nanoaggregate as the core and photosensitizer as the shell, has been constructed. Photosensitizers could be excited indirectly through a fluorescence resonance energy transfer (FRET) mechanism after the two-photon core was excited by a two-photon laser. The FRET efficiency was extremely high, owing to sufficient energy donors and stable energy acceptors. In this way, a photosensitizer could induce two-photon toxicity for improving the treatment depth in PDT. The nanocomplexes were prepared through a molecular assembly method, which avoided complicated reactions for synthesizing two-photon photosensitizers. The assembly method would expand the selection of photosensitizers and two-photon dyes, and endow traditional photosensitizers with a larger two-photon absorption cross-section for TP-PDT.

We designed a system for the controlled directional movements of kinesin-driven microtubule by restricting the motor coating areas in a two-dimensional (2D) substrate. The t-butoxycarbonyl (Boc) was firstly introduced in an amine groups modified glass surface to construct 2D track. The polarity of the above mentioned glass can be efficiently reversed after Boc protection, resulting in the surface transferring from hydrophilicity to hydrophobicity. Through a selective treatment of Boc de-protection, the substrate surface can be distributed into hydrophilic and hydrophobic partitions. The hydrophilic areas can be observed by labeling nanoparticles or fluorescent dye, thus the different shapes were formed at the substrate. The hydrophilic parts in the substrates will allow kinesin to be selectively immobilized on this surface and result in the controlled directional movement of microtubule. With this design, the selective decoration of 2D tracks may have a potential application in field of biomolecular motors based nanodevice.

Self-reproduction is one of the most important characteristics of lipid vesicles for origin of life research. Most vesicle self-reproduction systems are based on fatty acid vesicles and spontaneous phospholipid vesicle production is difficult owing to the relatively high stability of these vesicles. Now, spontaneous phospholipid vesicle generation and extension in a dipeptide/phospholipid system is demonstrated. Dissolution of the dipeptide crystal provides both the driving force and phospholipid constituents for vesicle generation and extension. This study provides a new system to enhance the understanding of vesicle self-reproduction mechanisms.

The microtubule-kinesin system is used to form microtubule-based structures via microtubule gliding motility. On the kinesin-coated surface, the microtubules can be easily assembled into stable micro- and nanostructures like circles and microtubule bundles using the streptavidin-biotin system. Furthermore, these microtubules structures can still retain performance with kinesin motor movement in spite of different velocities. Collisions bear responsibility for the majority of events leading to circle formation. By taking advantage of biological substances, some micro- or nanostructures, which are difficult to fabricate by artificial processes, can be easily obtained.

A natural-artificial hybrid system was constructed to enhance photophosphorylation. The system comprises chloroplasts modified with optically matched quantum dots (chloroplast-QD) with a large Stokes shift. The QDs possess a unique optical property and transform ultraviolet light into available and highly effective red light for use by chloroplasts. This favorable feature enables photosystem II contained within the hybrid system to split more water and produce more protons than chloroplasts would otherwise do on their own. Consequently, a larger proton gradient is generated and photophosphorylation is improved. At optimal efficiency activity increased by up to 2.3 times compared to pristine chloroplasts. Importantly, the degree of overlap between emission of the QDs and absorption of chloroplasts exerts a strong influence on the photophosphorylation efficiency. The chloroplast-QD hybrid presents an efficient solar energy conversion route, which involves a rational combination of a natural system and an artificial light-harvesting nanomaterial.

An azobenzene with a terminal formyl group, named as (4-[(3-Formyl-4-hydroxy)phenylazo]benzene (FHPAB)), was synthesized and used to manipulate the self-assembly of diphenylalanine (FF) molecules. Two-dimensional (2D) thin slices which are composed of ordered microspheres have been constructed through supramolecular self-assembly of FF and FHPAB. The FTIR and XPS results indicate that CN covalent bond between FF and FHPAB was generated. Hydrogen bonding and strong π-π interaction between the planar FF-HFPAB conjugates are the driving force to form the FF-HFPAB 2D thin slices. Based on the results, a possible formation mechanism of the 2D thin slices was proposed. We also found that the FF-based 2D thin slices possess superhydrophobic properties, which is therefore an extension of the range of applications of peptide assembly.

We report that templated by supramolecular assembly through electrostatic interaction and π-π stacking, one-dimensional gold hierarchical nanostructures are fabricated after chemical reduction in situ. It is found that through Ostwald ripening, such assembled complexes evolve from metastable nanospheres to stable microfibers. After reduction of these microfibers, one-dimensional gold hierarchical nanostructures composed of nanoparticles are obtained. Interestingly, the special hierarchical nanostructures exhibit different surface plasmon resonance property from conventional gold nanoparticles, having potential applications for photoelectronic devices. This work opens a new route to construct noble metal or their alloy nanostructures with hierarchy.

Dopamine-based materials are emerging as novel biomaterials and have attracted considerable interests in the fields of biosensing, bioimaging and cancer therapy due to their unique physicochemical properties, such as versatile adhesion property, high chemical reactivity, excellent biocompatibility and biodegradability, strong photothermal conversion capacity, etc. In this review, we present an overview of recent research progress on dopamine-based materials for diagnosis and therapy of cancer. The review starts with a summary of the physicochemical properties of dopamine-based materials in general. Then detailed description is followed on their applications in the fields of diagnosis and treatment of cancers. The review concludes with an outline of some remaining challenges for dopamine-based materials to be used for clinical applications.

Controlled growth of one-dimensional nanostructures is playing a key role in creating types of materials for functional devices. Here, we report procedures for controlled assembly of the dipeptide diphenylalanine (FF) into aligned and ultralong single crystals in a capillary. With the evaporation of solvent, nucleation of the crystal occurred in the confined region, and the crystal grew continuously with a supply of molecules from the concentration gradient system inside the capillary. Based on the "Knudsen regime", an ultralong aligned individual FF single crystal possessing an active optical waveguide property at macroscopic length scale could be obtained. Moreover, capillary is also an effective microdevice to investigate the disassembly process of the FF single crystals. This strategy has potentials to broaden the range of applications of aligned organic nanomaterials.

Secondary structures such as α-helix and β-sheet are the major structural motifs within the three-dimensional geometry of proteins. Therefore, structure transitions from β-sheet to α-helix not only can serve as an effective strategy for the therapy of neurological diseases through the inhibition of β-sheet aggregation but also extend the application of α-helix fibrils in biomedicine. Herein, we present a charge-induced secondary structure transition of amyloid-derived dipeptide assemblies from β-sheet to α-helix. We unravel that the electrostatic (charge) repulsion between the C-terminal charges of the dipeptide molecules are responsible for the conversion of the secondary structure. This finding provides a new perspective to understanding the secondary structure formation and transformation in the supramolecular organization and life activity.

Molecule assembly and functionalization of protocells have achieved a great success. However, the yield efficiency of photophosphorylation in the present cell-like systems is limited. Herein, inspired by natural photobacteria, we construct a protocell membrane reconstituting motor protein for highly efficient light-mediated adenosine triphosphate (ATP) synthesis through a layer-by-layer technique. The assembled membrane, compartmentally integrating photoacid generator, proton conductor, and ATP synthase, possesses excellent transparency, fast proton production, and quick proton transportation. Remarkably, these favorable features permit the formation of a large proton gradient in a confined region to drive ATP synthase to produce ATP with high efficiency (873 ATP s–1). It is the highest among the existing artificial photophosphorylation systems. Such a biomimetic system provides a bioenergy-supplying scenario for early photosynthetic life and holds promise in remotely controlled ATP-consumed biosensors, b...

Enhancing solar energy conversion efficiency is very important for developing renewable energy, protecting the environment, and producing agricultural products. Efficient enhancement of photophosphorylation is demonstrated by coupling artificial photoacid generators (PAGs) with chloroplasts. The encapsulation of small molecular long-lived PAGs in the thylakoid lumen is improved greatly by ultrasonication. Under visible-light irradiation, a fast intramolecular photoreaction of the PAG occurs and produces many protons, remarkably enhancing the proton gradient in situ. Consequently, compared to pure chloroplasts, the assembled natural-artificial hybrid demonstrates approximately 3.9 times greater adenosine triphosphate (ATP) production. This work will provide new opportunities for constructing enhanced solar energy conversion systems.

At present, one of main problems for photodynamic therapy (PDT) is how to improve the treatment depth. Two-photon activated (TPA) developed recently provide a possible solution for it. In this work, we report the energy-transferring assembled cationic dipeptide nanoparticles for two-photon activated photodynamic therapy (TPA-PDT). In the nanoparticles, the coencapsulated two-photon fluorescent dye bis(pyrene) (BP) is an energy donor, and a photosensitizer rose bengal (RB) is an acceptor based on an intraparticle fluorescence resonance energy transfer (FRET) mechanism. BP in the nanoparticles can be excited by one- or two- photon laser. And then, the energy of BP was transferred to RB, which highly enhanced the generation of singlet oxygen. The cellular experiments indicated that this nanosystem can induce the cytotoxicity under one- and two-photon irradiation, which allows further applications of FRET-based biomaterials for TPA-PDT.

Photosystem II (PSII) is a photoactive protein that can drive water oxidation under light irradiation. Recently, PSII has been broadly investigated with the high demand on the bioenergy. Here, we demonstrate a facile approach for the fabrication of a photoactive electrode by the integration of PSII with quantum dots (QDs)/polyelectrolyte multilayers. The assembled QDs and PSII film with a polyelectrolyte based substrate via layer-by-layer assembly can remain the photoactivity of the PSII and broaden the absorption spectrum of PSII to produce a high photocurrent yield. The co-assembly exhibits an obviously enhanced photocurrent under UV light irradiation. The proposed strategy can be considered for the reference and usage of PSII toward the solar energy conversion.

We report an environmentally-responsible limited hydrothermal reaction to construct gram-scale MnO2 sponge-like hierarchical nanostructures composed of ultrathin nanosheets (∼5 nm) in one pot. This template-free strategy simultaneously avoids the disposal of toxic materials and provides novel metal oxide nanostructures. As a typical application, the MnO2 hierarchical nanostructures prepared can easily remove positively-charged methylene blue in water with much more adsorption capacity than those of commercial carbon grain and MnO2 microparticles, TiO2 and Fe2O3 nanoparticles. Meanwhile, the solid–liquid separation is ready due to higher density resulted from their hierarchical nanostructures. Importantly adsorbed methylene blue can be reclaimed after elution with ethanol. Remarkably, the sponge-like hierarchical nanostructures can be recycled for many times with no obvious loss of adsorption capacity, qualifying them as a great potential application in environmental protection and resource reuse.

Photosystem II (PSII), as the only enzyme to catalyze the light-induced water oxidation reaction in the natural photosynthesis system, is introduced to fabricate artificial solar conversion systems with an intensive photo-to-current efficiency to convert solar energy into electrical power. In this research, we report a hybrid photo-bioelectrochemical system consisting of PSII isolated from spinach leaves that is co-assembled in nanotubular indium–tin oxide (ITO) multilayer films pasted on the commercial ITO substrate as a photoanode, which presents enhanced photocurrent responses as high as 2.4 μA cm−2 (mediator-free) and 39 μA cm−2 (with mediator) under white light irradiation (λ < 800 nm) using a xenon lamp as the light source. In this photoanode system, the three-dimensional (3D) hierarchical porous nanotubular ITO film was synthesized through a layer-by-layer (LBL) self-assembly process using a natural cellulose substance (e.g., filter paper) as a template. The specific structure, and good optical and electrical properties of the hierarchical nanotubular ITO allow for an increased protein loading as high as 166 pmol PSII cm−2 and an enhanced photocurrent by about 78 times compared with the bare PSII photoanode. This biomimetic template fabrication method of ITO materials with unique morphologies and desirable properties provides an effective assembly strategy for PSII-based hybrid photoanode systems for solar energy conversion.

Herein, we show that a molecular assembly offers tremendous opportunities of affording existing building units with new physicochemical properties, holding promise in wide applications. Herein, we develop a facile covalent assembly using a natural occurring linker, genipin, to efficiently transform a traditional chemo drug, doxorubicin, into a nanophotomedicine. A possible mechanism is proposed, in which doxorubicin reacts with genipin through covalent bonding to produce poorly soluble units, which further form nuclei and mediate the interfacial assembly to generate uniform nanoparticles. Such assembled nanophotomedicine shows remarkably enhanced singlet oxygen generation ability (about 1000 folds), leading to a much higher photodynamic activity. Moreover, this self-carried nanodrug exhibits adjustable size, excellent colloidal stability, high capacity and preferable endocytosis. These favorable features lead to greatly improved anticancer efficiency under light at the same dosage, compared to that of pure doxorubin. We believe this study brings a new dimension to develop advanced drug delivery systems by molecular assembly.

Polyelectrolyte multilayer capsules have become a novel and promising class of hybrid materials with great potential since they can be applied in various areas, such as pharmaceutical sciences, biotechnology, and biomedicine. The concept of using such carriers for biology application is diagnosis and treatment of diseases for convenience, safety and specific targeting. Therefore, the development of biocompatible, biodegradable and specific characteristic nanostructure material is highly desirable. Much effort has been devoted to exploring innovative and effective techniques to fabricate such materials. Among the available techniques, layer-by-layer (LbL) assembly capsules have attracted considerable attention attributing to the flexibly controlled size, shape, composition, wall thickness and functions. Protein, as the large class of biomacromolecules, was incorporated into capsules for improving the biocompatibility and specific function. In this review we provide an overview of the recent progress in biomacromolecular capsules or core/shell architecture with different diameters for the variety of purposes. The size ranging from micro-, sub-micro to nano scale based on the choice of the template. Their advantages are discussed here. The applications of these biomacromolecular capsules in biotechnological fields have also been summarized, for instance blood substitute, ATP carriers, photodynamic therapy and nanomedicines.

We explore a facile approach to construct dipeptide-based building blocks containing π-conjugated bridges by using biocross-linkers. Well-defined nanostructures can be assembled and tuned by using different solvents. Compared to pristine units, such dipeptide-based assemblies exhibit structure-dependent and remarkably enhanced optoelectronic properties.

Photodynamic therapy (PDT) has been used in the treatment of cancers and other benign diseases for several years in clinic. However, the hypoxia of tumors and the penetration limitation of excitation light to tissues can dramatically reduce the efficacy of PDT to cancers. To overcome these drawbacks, various assembled nanocarriers such as nanoparticles, nanocapsules, nanocrystals, and so on were introduced. The assembled nanocarriers have the ability of loading photosensitizers, delivering O2 into tumors, generating O2 in situ in tumors, as well as turning near-infrared (NIR) light, X-rays, and chemical energy into ultraviolet or visible light. Therefore, it is easy for the nanocarriers to improve the hypoxia microenvironment or increase the treatment depth of cancers, which will improve the efficiency of PDT to some degree. In recent years, a number of investigations were focused on these subjects. We will summarize the advances of nanocarriers in PDT, especially in O2 introduction PDT and deep PDT. The perspectives, challenges, and potential in translation of PDT will also be discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Bioinspired nanostructures can be the ideal functional smart materials to bridge the fundamental biology, biomedicine and nanobiotechnology fields. Among them, short peptides are among the most preferred building blocks as they can self-assemble to form versatile supramolecular architectures displaying unique physical and chemical properties, including intriguing optical features. Herein, we discuss the progress made over the past few decades in the design and characterization of optical short peptide nanomaterials, focusing on their intrinsic photoluminescent and waveguiding performances, along with the diverse modulation strategies. We review the complicated optical properties and the advanced applications of photoactive short peptide self-assemblies, including photocatalysis, as well as photothermal and photodynamic therapy. The diverse advantages of photoactive short peptide self-assemblies, such as eco-friendliness, morphological and functional flexibility, and ease of preparation and modification, endow them with the capability to potentially serve as next-generation, bio-organic optical materials, allowing the bridging of the optics world and the nanobiotechnology field.

Low biocompatibility or engineerability of conventional inorganic materials limits their extensive application for power harvesting in biological systems or at bio-machine interfaces. In contrast, intrinsically biocompatible peptide self-assemblies have shown promising potential as a new type of ideal components for eco-friendly optoelectronic energy-harvesting devices. However, the structural instability, weak mechanical strength, and inefficient optical or electrical properties severely impede their extensive application. Here, we demonstrate tryptophan-based aromatic dipeptide supramolecular structures to be direct wide-gap semiconductors. The molecular packings can be effectively modulated by changing the peptide sequence. The extensive and directional hydrogen bonding and aromatic interactions endow the structures with unique rigidity and thermal stability, as well as a wide-spectrum photoluminescence covering nearly the entire visible region, optical waveguiding, temperature/irradiation-dependent conductivity, and the ability to sustain quite high external electric fields. Furthermore, the assemblies display high piezoelectric properties, with a measured open-circuit voltage of up to 1.4 V. Our work provides insights into using aromatic short peptide self-assemblies for the fabrication of biocompatible, miniaturized electronics for power generation with tailored semiconducting optoelectronic properties and improved structural stability.

Molecular machines are an important and emerging frontier in research encompassing interdisciplinary subjects of chemistry, physics, biology, and nanotechnology. Although there has been major interest in creating synthetic molecular machines, research on natural molecular machines is also crucial. Biomolecular motors are natural molecular machines existing in nearly every living systems. They play a vital role in almost every essential process ranging from intracellular transport to cell division, muscle contraction and the biosynthesis of ATP that fuels life processes. The construction of biomolecular motor-based biomimetic systems can help not only to deeply understand the mechanisms of motor proteins in the biological process but also to push forward the development of bionics and biomolecular motor-based devices or nanomachines. From combination of natural biomolecular motors with supramolecular chemistry, great opportunities could emerge toward the development of intelligent molecular machines and biodevices. In this Account, we describe our efforts to design and reconstitute biomolecular motor-based active biomimetic systems, in particular, the combination of motor proteins with layer-by-layer (LbL) assembled cellular structures. They are divided into two parts: (i) reconstitution of rotary molecular motor F

Photothermal therapy (PTT) based on photothermal effect of the gold nanostructures, has been widely applied as a noninvasive therapy approach in cancer treatment. However, bare Au nanoparticles are not stable enough during the irradiation process, and cannot harvest sufficient energy to kill tumor cells. To improve this, we have fabricated a stable bioagent by loading gold nanorods (AuNRs) into multicompartment mesoporous silica nanoparticles (MMSNs) for the photothermal therapy. The procedure is that when AuNRs entrapped in MMSNs are irradiated by a laser in the near-infrared region of 808 nm, the hyperthermia produced by the assembled composites is strong enough to damage tumor tissues directly. Both experiments in vitro and in vivo demonstrate that the nanocomposites are perfect candidates as PTT agents for the cancer treatment with a high efficiency. Furthermore, it is found that the nanocomposites have good photostability and consistent temperature fluctuation over 11 on/off cycles with irradiation which the pure AuNRs will not have.

As a noninvasive treatment, photodynamic therapy (PDT) is a promising strategy against tumors. It is based on photosensitizer (PS)-induced phototoxicity after irradiation. However, most clinically approved PSs will be widely distributed in normal tissues, especially in the skin, where they will induce phototoxicity on exposure to light. Therefore, patients must remain in a dark room for up to several weeks during or after a PDT. Herein, we proposed a strategy of aggregation-induced emission PSs (AIE-PSs) entrapped in liposomes with controlled photosensitization. The AIE-PSs begin to lose their photosensitivity when entrapped in liposomes. After liposomes have carried AIE-PSs into tumor tissues, the AIE-PSs will be released and immediately reaggregate in a targeted area as the liposomes are decomposed. Their photosensitivity can be triggered at turn-on state and induce cytotoxicity. Two different types of AIE molecules were synthesized and entrapped by liposomes, respectively, to verify the PDT features against tumors in vitro and in vivo. The results indicate that, using this strategy, the photosensitivity of AIE-PS can be controlled and PDT can be treated under normal working conditions, not necessarily in a dark room.

Layer-by-layer (LbL) assembly is a most commonly used method to prepare various microcapsules based on the electrostatic interactions, hydrogen bonding, covalent bonding, and so on. Among these interactions, Schiff base bond formed in covalent assembly not only has an advantage in stability, but also enables the assembled microcapsules with autofluorescence and pH sensitivity. In this Article, we will mainly describe the construction of biomimetic microcapsules through Schiff base mediated LbL assembly. The structures and properties of the assembled microcapsules are introduced and their applications as drug carriers are highlighted.

Peptide assemblies are ideal components for eco-friendly optoelectronic energy harvesting devices due to their intrinsic biocompatibility, ease of fabrication, and flexible functionalization. However, to date, their practical applications have been limited due to the difficulty in obtaining stable, high-performance devices. Here, it is shown that the tryptophan-based simplest peptide cycloglycine-tryptophan (cyclo-GW) forms mechanically robust (elastic modulus up to 24.0 GPa) and thermally stable up to 370 °C monoclinic crystals, due to a supramolecular packing combining dense parallel β-sheet hydrogen bonding and herringbone edge-to-face aromatic interactions. The directional and extensive driving forces further confer unique optical properties, including aggregation-induced blue emission and unusual stable photo-luminescence. Moreover, the crystals produce a high and sustained opencircuit voltage (1.2 V) due to a high piezoelectric coefficient of 14.1 pC N(−1). These findings demonstrate the feasibility of utilizing self-assembling peptides for fabrication of biointegrated microdevices that combine high structural stability, tailored optoelectronics, and significant energy harvesting properties.

The formation of ordered nanostructures by metabolites is gaining increased interest due to the simplicity of the building blocks and their natural occurrence. Specifically, aromatic amino acids possess the ability to form ordered supramolecular interactions due to their limited solubility in aqueous solution. Unexpectedly, l-tyrosine (l-Tyr) is almost 2 orders of magnitude less soluble in water compared to l-phenylalanine (l-Phe). However, the underlying mechanism is not fully understood as l-Tyr is more polar. Here, we explore the utilization of insoluble tyrosine assemblies for technological applications and their molecular basis by manipulating the basic building blocks of tightly packed dimers. We show that the addition of an amyloid inhibition agent increases l-Tyr solubility due to the disruption of the dimer formation. The molecular organization grants the l-Tyr crystal higher thermal stability and mechanical properties between three amino acids. Additionally, l-Tyr crystals are shown to generate high and stable piezoelectric power outputs under mechanical pressure in a sandwich device. By incorporating the rigid l-Tyr crystals into a soft polymer, a mechano-responsive bending composite was fabricated. Furthermore, the l-Tyr crystalline needles exhibit an active photowaveguiding property, making them promising candidates for the generation of photonic biomaterial-based devices. The present work exemplifies a feasible strategy to explore physical properties of supramolecular self-assemblies comprises minimalistic naturally occurring building blocks and their applications in energy harvesting, photonic devices, stretchable electronics, and soft robotics.

Herein, we report on the unidirectional branched assembly of diphenylalanine dipeptide through a one-step rapid evaporation process. Large numbers of crystalline tubular branches with smooth surfaces are developed from a hexagonal solid microrod mimicking a "Christmas tree". Density functional theory suggests the formation of tubular diphenylalanine aggregates with cis isomers. The diphenylalanine branched assembly shows good optical waveguide properties that can transmit light homogeneously along the crystal fibers as well as harvest light from the tips of branches to the microrod terminals. These findings hold importance in the development of bioinspired optical fibers for information transmission in a microscale.

Prototypes of natural biosystems provide opportunities for artificial biomimetic systems to break the limits of natural reactions and achieve output control. However, mimicking unique natural structures and ingenious functions remains a challenge. Now, multiple biochemical reactions were integrated into artificially designed compartments via molecular assembly. First, multicompartmental silica nanoparticles with hierarchical structures that mimic the chloroplasts were obtained by a templated synthesis. Then, photoacid generators and ATPase-liposomes were assembled inside and outside of silica compartments, respectively. Upon light illumination, protons produced by a photoacid generator in the confined space can drive the liposome-embedded enzyme ATPase towards ATP synthesis, which mimics the photophosphorylation process in vitro. The method enables fabrication of bioinspired nanoreactors for photobiocatalysis and provides insight for understanding sophisticated biochemical reactions.

Surface engineering of synthetic carriers is an essential and important strategy for drug delivery in vivo. However, exogenous properties make synthetic nanosystems invaders that easily trigger the passive immune clearance mechanism, increasing the retention effect caused by the reticuloendothelial systems and bioadhesion, finally leading to low therapeutic efficacy and toxic effects. Recently, a cell membrane cloaking technique has been reported as a novel interfacing approach from the biological/immunological perspective, and has proved useful for improving the performance of synthetic nanocarriers in vivo. After cell membrane cloaking, nanoparticles not only acquire the physiochemical properties of natural cell membranes but also inherit unique biological functions due to the presence of membrane-anchored proteins, antigens, and immunological moieties. The derived biological properties and functions, such as immunosuppressive capability, long circulation time, and targeted recognition integrated in synthetic nanosystems, have enhanced their potential in biomedicine in the future. Here, we review the cell membrane-covered nanosystems, highlight their novelty, introduce relevant biomedical applications, and describe the future prospects for the use of this novel biomimetic system constructed from a combination of cell membranes and synthetic nanomaterials.