Self‐Assembled Peptide‐Based Nanomaterials for Biomedical Imaging and Therapy

Peptide‐based materials are one of the most important biomaterials, with diverse structures and functionalities. Over the past few decades, a self‐assembly strategy is introduced to construct peptide‐based nanomaterials, which can form well‐controlled superstructures with high stability and multivalent effect. More recently, peptide‐based functional biomaterials are widely utilized in clinical applications. However, there is no comprehensive review article that summarizes this growing area, from fundamental research to clinic translation. In this review, the recent progress of peptide‐based materials, from molecular building block peptides and self‐assembly driving forces, to biomedical and clinical applications is systematically summarized. Ex situ and in situ constructed nanomaterials based on functional peptides are presented. The advantages of intelligent in situ construction of peptide‐based nanomaterials in vivo are emphasized, including construction strategy, nanostructure modulation, and biomedical effects. This review highlights the importance of self‐assembled peptide nanostructures for nanomedicine and can facilitate further knowledge and understanding of these nanosystems toward clinical translation.     

Photoresponsive Self‐Assembled DNA Nanomaterials: Design,Working Principles,and Applications

Photoresponsive DNA nanomaterials represent a new class of remarkable functional materials. By adjusting the irradiation wavelength, light intensity, and exposure time, various photocontrolled DNA‐based systems can be reversibly or irreversibly regulated in respect of their size, shape, conformation, movement, and dissociation/association. This Review introduces the most updated progress in the development of photoresponsive DNA‐based system and emphasizes their advantages over other stimuli‐responsive systems. Their design and mechanisms to trigger the photoresponses are shown and discussed. The potential application of these photon‐responsive DNA nanomaterials in biology, biomedicine, materials science, nanophotonic and nanoelectronic are also covered and described. The challenges faced and further directions of the development of photocontrolled DNA‐based systems are also highlighted.     

Controlling the Diameters of Nanotubes Self‐Assembled from Designed Peptide Bolaphiles

Controlling the diameters of nanotubes represents a major challenge in nanostructures self‐assembled from templating molecules. Here, two series of bolaform hexapeptides are designed, with Set I consisting of Ac‐KI₄K‐NH₂, Ac‐KI₃NleK‐NH₂, Ac‐KI₃LK‐NH₂ and Ac‐KI₃TleK‐NH₂, and Set II consisting of Ac‐KI₃VK‐NH₂, Ac‐KI₂V₂K‐NH₂, Ac‐KIV₃K‐NH₂ and Ac‐KV₄K‐NH₂. In Set I, substitution for Ile in the C‐terminal alters its side‐chain branching, but the hydrophobicity is retained. In Set II, the substitution of Val for Ile leads to the decrease of hydrophobicity, but the side‐chain β‐branching is retained. The peptide bolaphiles tend to form long nanotubes, with the tube shell being composed of a peptide monolayer. Variation in core side‐chain branching and hydrophobicity causes a steady shift of peptide nanotube diameters from more than one hundred to several nanometers, thereby achieving a reliable control over the underlying molecular self‐assembling processes. Given the structural and functional roles of peptide tubes with varying dimensions in nature and in technological applications, this study exemplifies the predictive templating of nanostructures from short peptide self‐assembly.     

Self‐Assembled Biomimetic Capsules for Self‐Preservation

The inorganic semiconductor is an attractive material in sewage disposal and solar power generation. The main challenges associated with environment‐sensitive semiconductors are structural degradation and deactivation caused by the unfavorable environment. Here, inspired by the pomegranate, a self‐protection strategy based on the self‐assembly of silver chloride (AgCl) particles is reported. The distributed photosensitive AgCl particles can be encapsulated by themselves through mixing aqueous silver nitrate and protic ionic liquids (PILs). A probable assembling mechanism is proposed based on the electrostatic potential investigation of PILs cations. The AgCl particles inside the shell maintain their morphology and structure well after 6 months light‐treatment. Moreover, they exhibit excellent photocatalytic activity, same as newly prepared AgCl particles, for degradation of methyl orange (MO), neutral red (NR), bromocresol green (BG), rhodamine B (RhB), Congo red (CR), and crystal violet (CV).     

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.     

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.     

Electrostatic Control of Structure in Self‐Assembled Membranes

Self‐assembling peptide amphiphiles (PAs) can form hierarchically ordered membranes when brought in contact with aqueous polyelectrolytes of the opposite charge by rapidly creating a diffusion barrier composed of filamentous nanostructures parallel to the plane of the incipient membrane. Following this event, osmotic forces and charge complexation template nanofiber growth perpendicular to the plane of the membrane in a dynamic self‐assembly process. In this work, we show that this hierarchical structure requires massive interfacial aggregation of PA molecules, suggesting the importance of rapid diffusion barrier formation. Strong PA aggregation is induced here through the use of heparin‐binding PAs with heparin and also with polyelectrolytes of varying charge density. Small angle X‐ray scattering shows that in the case of weak PA‐polyelectrolyte interaction, membranes formed display a cubic phase ordering on the nanoscale that likely results from clusters of PA nanostructures surrounded by polyelectrolyte chains.     

White‐Emissive Self‐Assembled Organic Microcrystals

Organic semiconductor micro‐/nanocrystals with regular shapes have been demonstrated for many applications, such as organic field‐effect transistors, organic waveguide devices, organic solid‐state lasers, and therefore are inherently ideal building blocks for the key circuits in the next generation of miniaturized optoelectronics. In the study, blue‐emissive organic molecules of 1,4‐bis(2‐methylstyryl)benzene (o‐MSB) can assemble into rectangular microcrystals at a large scale via the room‐temperature solution‐exchange method. Because of the Förster resonance energy transfer, the energy of the absorbed photons by the host matrix organic molecules of o‐MSB can directly transfer to the dopant organic molecules of tetracene or 1,2:8,9‐dibenzopentacene (DBP), which then emit visible photons in different colors from blue to green, and to yellow. More impressively, by modulating the doping molar ratios of DBP to o‐MSB, bright white‐emissive organic microcrystals with well‐preserved rectangular morphology can be successfully achieved with a low doping ratio of 1.5%. These self‐assembled organic semiconductor microcrystals with multicolor emissions can be the white‐light sources for the integrated optical circuits at micro‐/nanoscale.     

Self‐Assembled Large Au Nanoparticle Arrays with Regular Hot Spots for SERS

The cost‐effective self‐assembly of 80 nm Au nanoparticles (NPs) into large‐domain, hexagonally close‐packed arrays for high‐sensitivity and high‐fidelity surface‐enhanced Raman spectroscopy (SERS) is demonstrated. These arrays exhibit specific optical resonances due to strong interparticle coupling, which are well reproduced by finite‐difference time‐domain (FDTD) simulations. The gaps between NPs form a regular lattice of hot spots that enable a large amplification of both photoluminescence and Raman signals. At smaller wavelengths the hot spots are extended away from the minimum‐gap positions, which allows SERS of larger analytes that do not fit into small gaps. Using CdSe quantum dots (QDs) a 3–5 times larger photoluminescence enhancement than previously reported is experimentally demonstrated and an unambiguous estimate of the electromagnetic SERS enhancement factor of ≈10⁴ is obtained by direct scanning electron microscopy imaging of QDs responsible for the Raman signal. Much stronger enhancement of ≈10⁸ is obtained at larger wavelengths for benzenethiol molecules penetrating the NP gaps.     

Self‐Assembled Metal–Phenolic Networks on Emulsions as Low‐Fouling and pH‐Responsive Particles

Interfacial self‐assembly is a powerful organizational force for fabricating functional nanomaterials, including nanocarriers, for imaging and drug delivery. Herein, the interfacial self‐assembly of pH‐responsive metal–phenolic networks (MPNs) on the liquid–liquid interface of oil‐in‐water emulsions is reported. Oleic acid emulsions of 100–250 nm in diameter are generated by ultrasonication, to which poly(ethylene glycol) (PEG)‐based polyphenolic ligands are assembled with simultaneous crosslinking by metal ions, thus forming an interfacial MPN. PEG provides a protective barrier on the emulsion phase and renders the emulsion low fouling. The MPN‐coated emulsions have a similar size and dispersity, but an enhanced stability when compared with the uncoated emulsions, and exhibit a low cell association in vitro, a blood circulation half‐life of ≈50 min in vivo, and are nontoxic to healthy mice. Furthermore, a model anticancer drug, doxorubicin, can be encapsulated within the emulsion phase at a high loading capacity (≈5 fg of doxorubicin per emulsion particle). The MPN coating imparts pH‐responsiveness to the drug‐loaded emulsions, leading to drug release at cell internalization pH and a potent cell cytotoxicity. The results highlight a straightforward strategy for the interfacial nanofabrication of pH‐responsive emulsion–MPN systems with potential use in biomedical applications.     

Aptamer‐Assembled Nanomaterials for Biosensing and Biomedical Applications

Aptamers represent a class of single‐stranded DNA or RNA oligonucleotides that play important roles in biosensing and biomedical applications. However, aptamers can gain more flexibility as molecular recognition tools by taking advantage of the unique chemical and physical properties provided by nanomaterials. Such aptamer–nanomaterial conjugates are having an increasing impact in the fields of biosensing, bioimaging, and therapy. The recent advances and limitations of aptamer‐assembled nanomaterials in biosensing and biomedical applications are briefly introduced and discussed.