Xuehai Yan

Reversible Transitions between Peptide Nanotubes and Vesicle-Like Structures Including Theoretical Modeling Studies

Peptide-based self-assembling systems are increasingly attractive because of their wide range of applications in different fields. Peptide nanostructures are flexible with changes in the ambient conditions. Herein, a reversible shape transition between self-assembled dipeptide nanotubes (DPNTs) and vesicle-like structures is observed upon a change in the peptide concentration. SEM, TEM, AFM, and CD spectroscopy were used to follow this transition process. We show that dilution of a peptide-nanotube dispersion solution results in the formation of vesicle-like structures, which can then be reassembled into the nanotubes by concentrating the solution. A theoretical model describing this shape-transition phenomenon is presented to propose ways to engineer assembling molecules in order to devise other systems in which the morphology can be tuned on demand.

Solvent‐Induced Structural Transition of Self‐Assembled Dipeptide: From Organogels to Microcrystals

Organogels that are self-assembled from simple peptide molecules are an interesting class of nano- and mesoscale soft matter with simplicity and functionality. Investigating the precise roles of the organic solvents and their effects on stabilization of the formed organogel is an important topic for the development of low-molecular-weight gelators. We report the structural transition of an organogel self-assembled from a single dipeptide building block, diphenylalanine (L-Phe-L-Phe, FF), in toluene into a flower-like microcrystal merely by introducing ethanol as a co-solvent; this provides deeper insights into the phase transition between mesostable gels and thermodynamically stable microcrystals. Multiple characterization techniques were used to reveal the transitions. The results indicate that there are different molecular-packing modes formed in the gels and in the microcrystals. Further studies show that the co-solvent, ethanol, which has a higher polarity than toluene, might be involved in the formation of hydrogen bonds during molecular self-assembly of the dipeptide in mixed solvents, thus leading to the transition of organogels into microcrystals. The structural transformation modulated by the co-solvent might have a potential implication in controllable molecular self-assembly.

Simple Peptide-Tuned Self-Assembly of Photosensitizers towards Anticancer Photodynamic Therapy

Peptide-tuned self-assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide- or amphiphilic amino-acid-tuned self-assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on-demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy in vitro and in vivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light.

An Injectable Self‐Assembling Collagen–Gold Hybrid Hydrogel for Combinatorial Antitumor Photothermal/Photodynamic Therapy

An injectable and self-healing collagen-gold hybrid hydrogel is spontaneously formed by electrostatic self-assembly and subsequent biomineralization. It is demonstrated that such collagen-based hydrogels may be used as an injectable material for local delivery of therapeutic agents, showing enhanced antitumor efficacy.

Triggered release of insulin from glucose-sensitive enzyme multilayer shells.

A glucose-sensitive multilayer shell, which was fabricated by the layer-by-layer (LbL) assembly method, can be used as a carrier for the encapsulation and controlled release of insulin. In the present report, glucose oxidase (GOD) and catalase (CAT) were assembled on insulin particles alternately via glutaraldehyde (GA) cross-linking. The resulting core-shell system has been proven to be glucose-sensitive. When the external glucose was introduced, the release ratio of insulin from the protein multilayer can be increased observably. This is likely attributed to the catalysis interaction of CAT/GOD shells to glucose, which leads to the production of H(+) and thus drops the pH of the microenvironment. Under the acidic conditions, on the one hand, a part of C=N bond formed from Schiff base reaction can be broken and thus increasing the permeability of the capsule wall. On the other hand, the solubility of insulin can also be increased. The above factors may be the key control to increase the release of insulin from the multilayer. Therefore, such CAT/GOD multilayer may have a great potential as a glucose-sensitive release carrier for insulin, and may open the way for the further application of LbL capsules in the drug delivery and controlled release, etc.

Self-assembly of peptide-inorganic hybrid spheres for adaptive encapsulation of guests.

Adv. Mater. 2010, 22, 1283–1287 2010 WILEY-VCH Verlag G T IO N Self-assembly, a common process at all scales, is emerging as a powerful, bottom-up approach for the fabrication of novel functional nanoor biomaterials. It is ubiquitous in nature. By learning from nature or imitating the self-assembly process in biological systems, one can delicately design or extract molecular building blocks for the creation of biomimetic or bioinspired nanostructural materials. Many bioactive building blocks for self-assembly are derived with inspiration from a pathogenic process. A known example is that of the diphenylalanine peptide (L-Phe-L-Phe) (FF) which is extracted from Alzheimer’s b-amyloid polypeptide as the core recognitionmotif for molecular self-assembly. Such peptides are a sort of versatile, selfassembling building block in the construction of defined supramolecular structures, owing to their ease of synthesis, facile chemical and biological modification, and biocompatibility. However, improved properties and novel functions for such nanoor biomaterials are needed to arrive at potential applications in nanotechnology. The fabrication of hybrid, supramolecular systems based on the combination of peptide or protein building blocks and inorganic components is an effective strategy to achieve the integration of functions. Herein, polyoxometalates (POMs), a well-known class of anionic oxide nanoclusters of transition metals, are used as possible inorganic components for the fabrication of such hybrid materials, owing to their potential applications in catalysis, electronics, optics, magnetic materials, medicine, and biology. We selected a Keggin-type POM, phosphotungstic acid (PTA) as a polyoxoanion model molecule, and combined it with the cationic dipeptide (CDP), H-Phe-Phe-NH2 HCl, which is derived from the FF peptide to assemble the expected hybrids. Figure 1 shows the suggested process of the formation of such functional hybrid colloidal spheres from the coassembly of PTA and CDP in water. To our knowledge, this is the first time that a stable, spherical structure has been obtained in water, based on the coassembly of a bioactive peptide and a polyoxoanion. The as-prepared colloidal spheres not only display stimuli-responsive properties to pH or temperature, but also lead to a novel function: enabling adaptive encapsulation for a wide variety of guest materials ranging from small molecules to nanoscale materials during self-assembly. The supramolecular assembly in the form of colloidal spheres based on PTA and CDP was initially investigated and prepared by the addition of an aqueous solution of PTA to a 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solution of CDP (in a 1:5 charge ratio) at room temperature. Such a mixing resulted in an immediate, opalescent, cloudy suspension (Fig. S1a in the Supporting Information), indicating there was some assembly taking place in the system. The precipitates, which were separated from the bulky solution, were imaged using scanning electron microscopy (SEM). An SEM image (Fig. 2a) shows that the assemblies are colloidal spheres with diameters ranging from about 100 to 250 nm. Energy dispersive X-ray (EDX) spectroscopy attached to the SEM (inset in Fig. 2a) indicates that such hybrid colloidal spheres are composed of both PTA and CDP, as evidenced by the presence of tungsten and carbon elements throughout the assemblies. Transmission electron microscopy (TEM) images (Fig. 2b–c) also demonstrate the formation of regular spherical structures with average diameters of 150 nm. The high-resolution TEM (HR-TEM) studies indicate that the hybrid colloidal spheres contain basic structural units consisting of many dark objects approximately 1 nm in size (attributable to single PTA clusters) surrounded by a peptide shell with lower electron contrast (Fig. 2d). The average size of the peptide-encapsulated clusters (PECs) is about 1.4 nm. It is noted that the diameter of each POM molecule with a Keggin structure is around 1 nm. In a dynamic light scattering (DLS) measurement

Peptide self-assembly: thermodynamics and kinetics

Self-assembling systems play a significant role in physiological functions and have therefore attracted tremendous attention due to their great potential for applications in energy, biomedicine and nanotechnology. Peptides, consisting of amino acids, are among the most popular building blocks and programmable molecular motifs. Nanostructures and materials assembled using peptides exhibit important potential for green-life new technology and biomedical applications mostly because of their bio-friendliness and reversibility. The formation of these ordered nanostructures pertains to the synergistic effect of various intermolecular non-covalent interactions, including hydrogen-bonding, π-π stacking, electrostatic, hydrophobic, and van der Waals interactions. Therefore, the self-assembly process is mainly driven by thermodynamics; however, kinetics is also a critical factor in structural modulation and function integration. In this review, we focus on the influence of thermodynamic and kinetic factors on structural assembly and regulation based on different types of peptide building blocks, including aromatic dipeptides, amphiphilic peptides, polypeptides, and amyloid-relevant peptides.

Biological Photothermal Nanodots Based on Self-Assembly of Peptide–Porphyrin Conjugates for Antitumor Therapy

Photothermal agents can harvest light energy and convert it into heat, offering a targeted and remote-controlled way to destroy carcinomatous cells and tissues. Inspired by the biological organization of polypeptides and porphyrins in living systems, here we have developed a supramolecular strategy to fabricate photothermal nanodots through peptide-modulated self-assembly of photoactive porphyrins. The self-assembling nature of porphyrins induces the formation of J-aggregates as substructures of the nanodots, and thus enables the fabrication of nanodots with totally inhibited fluorescence emission and singlet oxygen production, leading to a high light-to-heat conversion efficiency of the nanodots. The peptide moieties not only provide aqueous stability for the nanodots through hydrophilic interactions, but also provide a spatial barrier between porphyrin groups to inhibit the further growth of nanodots through the strong π-stacking interactions. Thermographic imaging reveals that the conversion of light to heat based on the nanodots is efficient in vitro and in vivo, enabling the nanodots to be applied for photothermal acoustic imaging and antitumor therapy. Antitumor therapy results show that these nanodots are highly biocompatible photothermal agents for tumor ablation, demonstrating the feasibility of using bioinspired nanostructures of self-assembling biomaterials for biomedical photoactive applications.

Preparation of Graphene Oxide-Based Hydrogels as Efficient Dye Adsorbents for Wastewater Treatment

Graphene oxide (GO) sheets exhibit superior adsorption capacity for removing organic dye pollutants from an aqueous environment. In this paper, the facile preparation of GO/polyethylenimine (PEI) hydrogels as efficient dye adsorbents has been reported. The GO/PEI hydrogels were achieved through both hydrogen bonding and electrostatic interactions between amine-rich PEI and GO sheets. For both methylene blue (MB) and rhodamine B (RhB), the as-prepared hydrogels exhibit removal rates within about 4 h in accordance with the pseudo-second-order model. The dye adsorption capacity of the hydrogel is mainly attributed to the GO sheets, whereas the PEI was incorporated to facilitate the gelation process of GO sheets. More importantly, the dye-adsorbed hydrogels can be conveniently separated from an aqueous environment, suggesting potential large-scale applications of the GO-based hydrogels for organic dye removal and wastewater treatment.

Self-Assembled Peptide- and Protein-Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy

Tremendous interest in self-assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self-assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self-assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self-assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non-covalent interactions, strategies, and the nanoarchitectures of self-assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in-depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self-assembly in improving the efficiency of photodynamic and photothermal therapy.