Guizhi Shen

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.

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.

Interfacial Cohesion and Assembly of Bioadhesive Molecules for Design of Long-Term Stable Hydrophobic Nanodrugs toward Effective Anticancer Therapy

The majority of anticancer drugs are poorly water-soluble and thus suffer from rather low bioavailability. Although a variety of delivery carriers have been developed for bioavailability improvement, they are severely limited by low drug loading and undesired side effects. The optimum delivery vehicle would be a biocompatible and biodegradable drug nanoparticle of uniform size with a thin but stable shell, making it soluble, preventing aggregation and enabling targeting. Here, we present a general strategy for the rational design of hydrophobic drug nanoparticles with high drug loading by means of interfacial cohesion and supramolecular assembly of bioadhesive species. We demonstrate that the pathway is capable of effectively suppressing and retarding Ostwald ripening, providing drug nanoparticles with small and uniform size and long-term colloidal stability. The final complex drug nanoparticles provide higher tumor accumulation, negligible toxicity, and enhanced antitumor activity, superior to commercial formulations. Our findings demonstrate that local, on-demand coating of hydrophobic nanoparticles is achievable through cooperation and compromise of interfacial adhesion and assembly.

Fabrication of Au@Pt Multibranched Nanoparticles and Their Application to In Situ SERS Monitoring

Here, we present an Au@Pt core-shell multibranched nanoparticle as a new substrate capable of in situ surface-enhanced Raman scattering (SERS), thereby enabling monitoring of the catalytic reaction on the active surface. By careful control of the amount of Pt deposited bimetallic Au@Pt, nanoparticles with moderate performance both for SERS and catalytic activity were obtained. The Pt-catalyzed reduction of 4-nitrothiophenol by borohydride was chosen as the model reaction. The intermediate during the reaction was captured and clearly identified via SERS spectroscopy. We established in situ SERS spectroscopy as a promising and powerful technique to investigate in situ reactions taking place in heterogeneous catalysis.

Water-Insoluble Photosensitizer Nanocolloids Stabilized by Supramolecular Interfacial Assembly towards Photodynamic Therapy

Nanoengineering of hydrophobic photosensitizers (PSs) is a promising approach for improved tumor delivery and enhanced photodynamic therapy (PDT) efficiency. A variety of delivery carriers have been developed for tumor delivery of PSs through the enhanced permeation and retention (EPR) effect. However, a high-performance PS delivery system with minimum use of carrier materials with excellent biocompatibility is highly appreciated. In this work, we utilized the spatiotemporal interfacial adhesion and assembly of supramolecular coordination to achieve the nanoengineering of water-insoluble photosensitizer Chlorin e6 (Ce6). The hydrophobic Ce6 nanoparticles are well stabilized in a aqueous medium by the interfacially-assembled film due to the coordination polymerization of tannic acid (TA) and ferric iron (Fe(III)). The resulting Ce6@TA-Fe(III) complex nanoparticles (referenced as Ce6@TA-Fe(III) NPs) significantly improves the drug loading content (~65%) and have an average size of 60 nm. The Ce6@TA-Fe(III) NPs are almost non-emissive as the aggregated states, but they can light up after intracellular internalization, which thus realizes low dark toxicity and excellent phototoxicity under laser irradiation. The Ce6@TA-Fe(III) NPs prolong blood circulation, promote tumor-selective accumulation of PSs, and enhanced antitumor efficacy in comparison to the free-carrier Ce6 in vivo evaluation.

Self-assembled Injectable Peptide Hydrogels Capable of Triggering Antitumor Immune Response

Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and antitumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures, and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly peptide (poly-l-lysine, PLL). Electrostatic coupling between PLL and a self-assembling dipeptide (Fmoc-FF) provides a smart switch to enable the fibrous hydrogels to be shear-thinning and self-healing, thus leading to the formation of supramolecular hydrogels with rheological properties suitable for injection. The latter can be flexibly adjusted by merely varying the concentration or the molecular weight of the polypeptide to satisfy a variety of requirements in biological applications. The hydrogels, consisting of helical nanofibers stabilized with disulfide bonds, are prepared and further injected for antitumor therapy. The results demonstrate that the helical fibrous hydrogel, without the addition of antigens, immune regulatory factors, and adjuvants, can activate T cell response and efficiently suppress tumor growth. Therefore, injectable hydrogels self-assembled by a combination of small peptides and biomacromolecules present a great potential for biomedical applications, especially for development of a new type of immuno-responsive materials toward antitumor therapy.

Engineering and delivery of nanocolloids of hydrophobic drugs

A lot of efforts have been devoted to engineering the delivery of hydrophobic drugs due to the high demand of chemotherapy against cancer. While early developed liposomes and polymeric nanoparticles did not meet the requirements of high drug loading efficiency, pure drug nanoparticles appeared to meet these together with high stability. Current drug delivery systems demand an improved performance over the whole aspects of stability, loading capacity, and therapeutic effects. As a result, both new techniques based on traditional methods and totally new procedures are under investigation. In this review, we focus on the evaluation of pure drug nanolloids fabricated by different engineering protocols with emphasis on the size and morphology, delivery and controlled release, and therapeutic effects of these drug nanocolloids.

Dipeptide concave nanospheres based on interfacially controlled self-assembly: from crescent to solid

Concave nanospheres based on the self-assembly of simple dipeptides not only provide alternatives for modeling the interactions between biomacromolecules, but also present a range of applications for purification and separation, and delivery of active species. The kinetic control of the peptide assembly provides a unique opportunity to build functional and dynamic nanomaterials, such as concave nanospheres. In this work, we report dipeptide-based concave nanospheres with structures from crescent-like to solid interior by interfacially controlled self-assembly in combination with covalent formation of building blocks, driven by synergistic thermodynamic and kinetic control. The thermodynamics of nucleation and assembly at the interfaces is governed by the gradual formation of bola-dipeptides (FF-GAn-FF), due to the covalent Schiffs base reaction between the glutaraldehyde (GA) and amino groups of diphenylalanine (FF), and non-covalent interactions of FF-GAn-FF building blocks for self-assembly. The kinetic growth process of concave nanospheres is determined by the formation rate of FF-GAn-FF bola-dipeptides and their interfacial nucleation rate. The concave nanospheres can be further functionalized easily by encapsulation of functional inorganic nanoparticles (e.g. magnetic nanoparticles) in the oil phase.

Hybridizing Carbon Nitride Colloids with a Shell of Water-Soluble Conjugated Polymers for Tunable Full-Color Emission and Synergistic Cell Imaging

We present the preparation of a new multicolor emission system constructed from two complementary conjugated materials that are highly photoluminescent, that is, phenyl-modified carbon nitride (PhCN) colloids as the core and water-soluble conjugated polymers (WSCPs) adsorbed as the shell. The fluorescence bands of the PhCN and WSCPs effectively complement each other and the overall emission can be simply adjusted to fully cover the visible light spectrum with white light emission also accessible. Photophysical insights imply that the interactions between PhCN and WSCPs preserve the binary system from emission distortion and degradation, which is essential to delicately tune the overall fluorescence bands. Notably, the continuously tunable emission color is achieved under single-wavelength excitation (365 nm). This hybrid shows a synergistic permeation performance in cell imaging, that is, PhCN nanoparticles help the WSCP to enter the cells and therefore multicolor cellular imaging achieved.