Qianli Zou

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.

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.

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.

Peptide-Modulated Self-Assembly of Chromophores toward Biomimetic Light-Harvesting Nanoarchitectonics

Elegant self-assembling complexes by the combination of proteins/peptides with functional chromophores are decisively responsible for highly efficient light-harvesting and energy transfer in natural photosynthetic systems. Mimicking natural light-harvesting complexes through synthetic peptides is attractive due to their advantanges of programmable primary structure, tunable self-assembly architecture and easy availability in comparison to naturally occuring proteins. Here, an overview of recent progresses in the area of biomimetic light-harvesting nanoarchitectonics based on peptide-modulated self-assembly of chromophores is provided. Adjusting the organization of chromophores, either by creating peptide-chromophore conjugates or by the non-covalent assembly of peptides and chromophores are highlighted. The light-harvesting properties, especially the energy transfer of the biomimetic complexes are critically discussed. The applications of such complexes in the mineralization of inorganic nanoparticles, generation of molecular hydrogen and oxygen, and photosynthesis of bioactive molecules are also included.

Peptide-Induced Hierarchical Long-Range Order and Photocatalytic Activity of Porphyrin Assemblies

Long-range structural order and alignment over different scales are of key importance for the regulation of structure and functionality in biology. However, it remains a great challenge to engineer and assemble such complex functional synthetic systems with order over different length scales from simple biologically relevant molecules, such as peptides and porphyrins. Herein we describe the successful introduction of hierarchical long-range order in dipeptide-adjusted porphyrin self-assembly by a thermodynamically driven self-orienting assembly pathway associated with multiple weak interactions. The long-range order and alignment of fiber bundles induced new properties, including anisotropic birefringence, a large Stokes shift, amplified chirality, and excellent photostability as well as sustainable photocatalytic activity. We also demonstrate that the aligned fiber bundles are able to induce the epitaxially oriented growth of Pt nanowires in a photocatalytic reaction.

Nanoengineering of Stimuli-Responsive Protein-Based Biomimetic Protocells as Versatile Drug Delivery Tools

We present a general strategy to nanoengineer protein-based colloidal spheres (biomimetic protocells) as versatile delivery carriers with stimuli responsiveness by the electrostatic assembly of binary components (proteins and polypeptides) in association with intermolecular disulfide cross-linking. The size of the colloidal spheres, ranging from nanoscale to microscale, is readily tuned through parameters like protein and polypeptide concentration, the ratio between both, pH, and so on. Moreover, such colloidal spheres show versatile encapsulation of various guest molecules including small organic molecules and biomacromolecules. The pH and redox dual-responsiveness facilitates the rapid release of the payload in an acidic and reductant-enriched ambient such as in lysosomes. Thus, nanoengineering of protein-based biomimetic protocells opens a new alternative avenue for developing delivery vehicles with multifunctional properties towards a range of therapeutic and diagnostic applications.

Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation

Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles.

Self-Assembled Zinc/Cystine-Based Chloroplast Mimics Capable of Photoenzymatic Reactions for Sustainable Fuel Synthesis

Prototypes of biosystems provide good blueprints for the design and creation of biomimetic systems. However, mimicking both the sophisticated natural structures and their complex biological functions still remains a great challenge. Herein, chloroplast mimics have been fabricated by one-step bioinspired amino acid mineralization and simultaneous integration of catalytically active units. Hierarchically structured crystals were obtained by the metal-ion-directed self-assembly of cystine (the oxidized dimer of the amino acid cysteine), with a porous structure and stacks of nanorods, which show similar architectural principles to chloroplasts. Porphyrins and enzymes can both be encapsulated inside the crystal during mineralization, rendering the crystal photocatalytically and enzymatically active for an efficient and sustainable synthesis of hydrogen and acetaldehyde in a coupled photoenzymatic reaction.

Amino Acid Coordinated Self‐Assembly

Self-assembly of highly important biomolecules, such as proteins and peptides, has attracted tremendous interest in supramolecular construction of functional materials. However, as proteins and peptides are often immunogenic and their structures are complex, there is a strong demand to use amino acids as simpler building blocks. Still, mimicking the sophisticated structures and functions of natural materials by self-assembly of simpler and more basic units of biomolecules, such as amino acids, remains a formidable challenge. Inspired by metal-ion-associated crystallization of l-cystine in the urinary system, amino acid coordinated self-assembly is discussed as an original strategy for supramolecular construction of biomimetic materials. The resulting materials possess the features of uniform size, hierarchical architecture, and structural resemblance to biological structures. In addition, the self-assembly process can readily be adapted to simultaneous integration of various functional modules, providing materials with promising properties for biomimetic and biomedical applications.

Smart Peptide-Based Supramolecular Photodynamic Metallo-Nanodrugs Designed by Multicomponent Coordination Self-Assembly

Supramolecular photosensitizer nanodrugs that combine the flexibility of supramolecular self-assembly and the advantage of spatiotemporal, controlled drug delivery are promising for dedicated, precise, noninvasive tumor therapy. However, integrating robust blood circulation and targeted burst release in a single photosensitizer nanodrug platform that can simultaneously improve the therapeutic performance and reduce side effects is challenging. Herein, we demonstrate a multicomponent coordination self-assembly strategy that is versatile and potent for the development of photodynamic nanodrugs. Inspired by the multicomponent self-organization of polypeptides, pigments, and metal ions in metalloproteins, smart metallo-nanodrugs are constructed based on the combination and cooperation of multiple coordination, hydrophobic, and electrostatic noncovalent interactions among short peptides, photosensitizers, and metal ions. The resulting metallo-nanodrugs have uniform sizes, well-defined nanosphere structures, and high loading capacities. Most importantly, multicomponent assembled nanodrugs have robust colloidal stability and ultrasensitive responses to pH and redox stimuli. These properties prolong blood circulation, increase tumor accumulation, and enhance the photodynamic tumor therapeutic efficacy. This study offers a new strategy to harness robust, smart metallo-nanodrugs with integrated flexibility and multifunction to enhance tumor-specific delivery and therapeutic effects, highlighting opportunities to develop next-generation, smart photosensitizing nanomedicines.