Peptide-Based Optical/Electronic Materials: Assembly and Recent Applications in Biomedicine, Sensing, and Energy Storage.

The unique optical and electronic properties of living systems are impressive. Peptide-based supramolecular self-assembly systems attempt to mimic these properties by preparation optical/electronic function materials with specific structure through simple building blocks, rational molecular design, and specific kinetic stimulation. From the perspective of building blocks and assembly strategies, the unique optical and electronic properties of peptide-based nanostructures, including peptides self-assembly and peptides regulate the assembly of external function subunits, are systematically reviewed. Additionally, their applications in biomedicine, sensing, and energy storage are also highlighted. This bioinspired peptide-based function material is one of the hot candidates for the new generation of green intellect materials, with many advantages such as biocompatibility, environmental friendliness, and adjustable morphology.

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.

Surface Self-Assembly of Dipeptides on Porous CaCO3 Particles Promoting Cell Internalization.

The self-assembling behavior of peptides and derivatives is crucial in the natural process to construct various architectures and achieve specific functions. However, the surface or interfacial self-assembly, in particular, on the surface of micro- or nanoparticles is even less systematically investigated. Here, uniform porous CaCO3 microparticles were prepared with different charged, hydrophobic and hydrophilic surfaces to assess the self-assembling behavior of dipeptides composed of various sequences. Experimental results indicate that dipeptides with a negative charge in an aqueous solution preferred to self-assemble on the hydrophobic and positively charged surface of CaCO3 particles, which can be ascribed to the electrostatic and hydrophobic interaction between dipeptides and CaCO3 particles. Meanwhile, the Log p (lipid-water partition coefficient) of dipeptides has a significant effect on the self-assembling behavior of dipeptides on the surface of porous CaCO3; dipeptides with high Log p preferred to self-assemble on the surface of CaCO3 particles, resulting in the improved cell internalization efficiency of particles with low cytotoxicity. After loading with a model drug (doxorubicin), the particles show obvious antitumor activity in animal experiments and can reduce Dox side effects effectively.

Long-range ordered amino acid assemblies exhibit effective optical-to-electrical transduction and stable photoluminescence.

Bio-endogenous peptide molecules are ideal components for fabrication of biocompatible and environmentally friendly semiconductors materials. However, to date, their applications have been limited due to the difficulty in obtaining stable, high-performance devices. Herein, simple amino acid derivatives fluorenylmethoxycarbonyl-leucine (Fmoc-L) and fluorenylmethoxycarbonyl-tryptophan (Fmoc-W) are utilized to form long-range ordered supramolecular nanostructures by tight aromatic stacking and extensive hydrogen bonding with mechanical, electrical and optical properties. For the first time, without addition of any photosensitizers, pure Fmoc-L microbelts and Fmoc-W microwires exhibit Young's modulus up to 28.79 and 26.96 GPa, and unprecedently high values of photocurrent responses up to 2.2 and 2.3 µA/cm2, respectively. Meanwhile, Fmoc-W microwires with stable blue fluorescent emission under continuous excitation are successfully used as LED phosphors. Mechanism analysis shows that these two amino acids derivatives firstly formed dimers to reduce the bandgap, then further assemble into bioinspired semiconductor materials using the dimers as the building blocks. In this process, aromatic residues of amino acids are more conducive to the formation of semiconducting characteristics than fluorenyl groups. STATEMENT OF SIGNIFICANCE: Long-range ordered amino acid derivative assemblies with mechanical, electrical and optical properties were fabricated by a green and facile biomimetic strategy. These amino acid assemblies have Young's modulus comparable to that of concrete and exhibit typical semiconducting characteristics. Even without the addition of any photosensitizer, pure amino acid assemblies can still produce a strong photocurrent response and an unusually stable photoluminescence. The results suggest that amino acid structures with hydrophilic C-terminal and aromatic residues are more conducive to the formation of semiconducting characteristics. This work unlocks the potential for amino acid molecules to self-assemble into high-performance bioinspired semiconductors, providing a reference for customized development of biocompatible and environmentally friendly semiconductor materials through rational molecular design.

In situ synthesis of superorganism-like Au NPs within microgels with ultra-wide absorption in visible and near-infrared regions for combined cancer therapy.

The whole is a collection of parts and fulfills specific functions that the parts do not have. In this work, 50 nm Au NPs were in situ synthesized and close packed into a superorganism-like superstructure by means of microgel 3D networks. The combined microgel is endowed with ultra-wide absorption in visible and near-infrared regions between 500 and 1100 nm in spite of Au NPs not having this property. The strong collective plasmon coupling between neighboring Au NPs induces high photothermal conversion efficiency of the microgel system under irradiation at various laser wavelengths. Due to the good loading capability, microgels with nanocomposites can also load photosensitive drugs simultaneously and be used for combined cancer treatments of photothermal therapy and photodynamic therapy.

Dipeptide Self-assembled Hydrogels with Shear-Thinning and Instantaneous Self-healing Properties Determined by Peptide Sequences.

Dipeptide self-assembled hydrogels have potential biomedical applications because of their great biocompatibility, bioactivity, and tunable physicochemical properties, which can be modulated in the molecular level by design of amino acid sequences. Herein, a series of dipeptides (Fmoc-FL, -YL, -LL, and -YA) are designed to form shear-thinning hydrogels with self-healing and tunable mechanical properties by adjusting the synergetic effect of hydrophobic interactions (π-π stacking and hydrophobic effect) and hydrogen bonds of peptides through substitution of amino acid residues. The enhancement of hydrophobic interactions is a primary factor to promote mechanical rigidity of hydrogels, and strong hydrogen-bonding interactions between molecules contribute to the instantaneous self-healing property, which is supported by experimental studies (FTIR, CD, SEM, AFM, and rheology) and molecular dynamics simulations. The injectable dipeptide hydrogels were certified as an ideal endoscopic submucosal dissection filler to make operation convenient and secure in mice and living mini-pig's experiments with a longer duration time, higher stiffness, and lower inflammatory response than commercial clinical fillers.

Peptide assembly assisted triplet-triplet annihilation photon upconversion in non-deoxygenated water.

Triplet-triplet annihilation upconversion (TTA-UC) has great potential in many fields. However, a stable TTA-UC system with adjustable UC efficiency in non-deoxygenated water is still in urgent demand. Here, the first example of short peptide-tuned UC luminescence in water is reported. With only a small amount of peptides, UC chromophores can assemble into tetrahedral microrods with adjustable size and UC efficiency. Successful TTA-UC luminescence of these microrods in water is achieved due to the regular and dense organization of molecular upconversion chromophores tuned by peptides, which allows rapid triplet exciton migration, avoids aggregation-induced quenching and screens molecular oxygen to upconversion chromophores.

Insight into the efficiency of oxygen introduced photodynamic therapy (PDT) and deep PDT against cancers with various assembled nanocarriers.

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.

Dipeptide Self-Assembled Hydrogels with Tunable Mechanical Properties and Degradability for 3D Bioprinting.

Supramolecular hydrogels self-assembled from short peptides have shown great potential as biomimetic extracellular matrices with controllable properties designed at the molecular level. However, their weak mechanical strength still remains a big challenge for 3D bioprinting. Herein, two oppositely charged dipeptides are designed and used as bioinks in a ″layer-by-layer″ alternative bioprinting strategy. During printing, in situ gelation is achieved by electrostatic interactions between two dipeptides without additional cross-linking procedures. The binary hydrogels have tunable mechanical properties with elastic moduli ranging from 4 to 62 kPa and controllable biodegradability from days to weeks, which can ideally mimic the natural environment of a variety of cell types. It is demonstrated that the hydrogel scaffold enables the formation, growth, and natural release of HepaRG spheroids with sizes up to millimeters. This strategy may be suitable to develop a series of new bioink materials based on peptides and other supramolecular polymers for 3D bioprinting.

Gold nanorods based multicompartment mesoporous silica composites as bioagents for highly efficient photothermal therapy.

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.

One-step co-assembly method to fabricate photosensitive peptide nanoparticles for two-photon photodynamic therapy.

Peptide-based nanoparticles were employed to load and disperse hydrophobic porphyrins in a one-step co-assembly method in aqueous media. The isolated porphyrins doped within nanoparticles showed enhanced two-photon absorption ability and could effectively generate 1O2 to induce the apoptosis of cancer cells, which holds great prospects in two-photon PDT.

Preparation of Microgels with Ultrahigh Payload of Various Hydrophilic and Hydrophobic Inorganic Nanoparticle Composites up to 92 wt.

Microgel loading with inorganic nanoparticle (NP) composites attracts interest for various biomedical applications. However, the encapsulation of NPs into microgels usually is a diffusion process driven by osmotic pressure, which depends highly on the concentration of NPs and causes low loading efficiency. In this work, we demonstrate preparation of microgels with ultrahigh content of various nano-objects (up to 92%, wt %) by a gelatin "casting" strategy using porous CaCO3 particles as templates. This approach could encapsulate various NPs with different charged, hydrophilic, and hydrophobic surfaces, shape, and size within microgels, without causing aggregation or change of physicochemical properties of NPs. The hybrid microgels coupled with properties of both inorganic NPs and hydrogels can be taken as an effective photothermal therapy system with great stability, reusability, and degradability and show high effective photothermal activity which is highly related to the content of NPs within microgels. The strategy of fabrication of microgels with nanocomposites is certified to be simple, facile, and low cost, which has potential applications in cancer therapy, drug delivery, catalysis, detecting system, and sewage treatment.

Supramolecularly Assembled Nanocomposites as Biomimetic Chloroplasts for Enhancement of Photophosphorylation.

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.

Self-Assembly of Monomeric Hydrophobic Photosensitizers with Short Peptides Forming Photodynamic Nanoparticles with Real-Time Tracking Property and without the Need of Release in Vivo.

Employing nanoscaled materials as photosensitizer (PS) carriers is an effective strategy to solve the problem of poor solubility and low tumor selectivity of hydrophobic PS in photodynamic therapy (PDT), which compulsorily requires the PS release in PDT implementation. However, the complicated environment in vivo makes it difficult to precisely design and control the release process and the delivery process requires real-time tracking. Developing a delivery strategy of hydrophobic PS in the monomeric form with fluorescent emission and without consideration of the PS release in the PDT process, is in urgent demand. Herein, we report a versatile and potent strategy for fabrication of photodynamic nanoparticles (nanoPSs) with featuring the monomeric PS based on aromatic peptide-modulated self-assembly of porphyrin derivatives. Aromatic peptides within nanoPSs can isolate hydrophobic porphyrins from each other, resulting in monomeric porphyrin delivery with real-time fluorescence tracking property and avoiding self-aggregation and hence porphyrin release. Moreover, partially charged porphyrins tend to expose on the surface of nanoPSs, facilitating production and diffusion of 1O2. The highest 1O2 yield can be achieved with porphyrin loading as low as 6 wt %, reducing side effects of excessive porphyrin injection. The nanoPSs show enhanced PDT efficacy in vitro and in vivo leading to complete tumor eradication. This study highlights opportunities for development of active photodynamic nanoparticles and provides an alternative strategy for delivery of hydrophobic photosensitive drugs with enhanced therapeutic effects.

Tuning Supramolecular Structure and Functions of Peptide bola-Amphiphile by Solvent Evaporation-Dissolution.

Solvent molecules significantly affect the supramolecular self-assembly, for example, in forming solvent-bridged hydrogen bonding networks. Even small changes in solvent composition can have dramatic impact on supramolecular assembly. Herein, we demonstrate the use of trace solvents (as low as 0.04%) to tune the morphology and consequent functions of supramolecular nanostructures based on an aromatic peptide bola-amphiphile. Specifically, perylene bisimide-(di)glycine-tyrosine (PBI-[GY]2) bola-amphiphile was shown to give rise to red-emitting nanofibers when assembled in water, while exposure to trace organic solvents such as tetrahydrofuran (THF) and others via solvent-evaporation followed by aqueous assembly gave rise to white-light-emitting nanospheres. Differential hydrogen bonding between water (donor and acceptor) and THF (acceptor only) impacts supramolecular organization, which was verified using a density functional theory (DFT) simulation. The tunable consequent surface hydrophobicity was utilized in staining the cytoplasm and membrane of cells, respectively. The trace-solvent effect achieved through evaporation-dissolution provides a methodology to mediate the morphologies and consequent functions for supramolecular biomaterials controlled by the self-assembly pathway.

Hyperbranched Polyglycerol-Induced Porous Silica Nanoparticles as Drug Carriers for Cancer Therapy In†Vitro and In†Vivo.

Mesoporous silica-based nanoparticles are generally accepted as a potential platform for drug loading with a lot of advantages, except for their complex purification procedures and structures that are difficult to decompose. In this work, biocompatible hyperbranched polyglycerol is introduced to synthesize mesoporous silica nanoparticles (MSNs). The materials possess good biocompatibility, controlled release, and biodegradability. They also show passive targeting capability through the enhanced permeability and retention effect and can be excreted from the biological system. The method avoids the needs to employ traditional surfactants and complicated purified procedures, which make these MSNs an efficient delivery system for cancer therapy.

Biomacromolecules based core/shell architecture toward biomedical applications.

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.

Solvothermally Mediated Self-Assembly of Ultralong Peptide Nanobelts Capable of Optical Waveguiding.

The formation of ultralong peptide crystalline nanobelts using a solvothermal approach from a di-phenylalanine gel within 10 min, where the self-assembly process is accelerated by several orders of magnitude compared with the month-long glutaraldehyde induction method previously reported, has been demonstrated. The solvothermal treatment can facilitate the phase separation of di-phenylalanine gels while speeding up the kinetics of the intramolecular cyclization reaction and concomitant crystallization. Moreover, the modulation effect of formaldehyde as an additive is revealed, and that a small amount of formaldehyde leads to thicker crystalline platelets capable of curved optical waveguiding that can potentially be applied in advanced bio-optical and optoelectronic devices, a rare feat with peptide-based crystals.

Fabrication of Mesoporous Silica Nanoparticle with Well-Defined Multicompartment Structure as Efficient Drug Carrier for Cancer Therapy in Vitro and in Vivo.

Vaterite particles are composed of particulate CaCO3 nanoparticles, which offer an ideal platform to synthesize architectures with hierarchical structure. Herein we show that mesoporous silica particles with well-defined multicompartment structure are fabricated by employing vaterite particles as templates. The obtained silica particles inherited the structure feature of vaterite and had excellent biocompatibility and biodegradability. Moreover, the silica particles were established as an efficient anticancer drugs carrier compared with hollow silica particles, which could be applied in cancer therapy in vitro and in vivo. The silica particles obtained here offer a cheap, facile, environmentally friendly avenue to assembly of hierarchical drugs carriers.

Layer by layer assembly of albumin nanoparticles with selective recognition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Crosslinked albumin nanoparticles which loaded with doxorubicin (DOX) were fabricated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and biocompatible polysaccharide, alginate (ALG), using layer-by-layer technique. Albumin nanoparticles exhibited narrow size distribution and fluorescent property. The assembled core/shell structure of the nanoparticles can be internalized more easily with the cancer cells, which attributes to TRAIL binding with death receptors. TRAIL still hold bioactive properties after assembled onto the particles. In addition, after loaded into the albumin core nanoparticles, DOX (as the chemotherapeutics) display a synergistic cytotoxic effect on cytotoxicity in combination with TRAIL in vitro. The core/shell nanostructured nanoparticles realized in this study would be used as a promising candidate for novel drug carriers.