Showing papers by "Weiwei Gao published in 2023"

Synthesis of Erythrocyte Nanodiscs for Bacterial Toxin Neutralization.

Abstract: Nanodiscs are a compelling nanomedicine platform due to their ultrasmall size and distinct disc shape. Current nanodisc formulations are made primarily with synthetic lipid bilayers and proteins. Here, we report a cellular nanodisc made with human red blood cell (RBC) membrane (denoted "RBC-ND") and show its effective neutralization against bacterial toxins. In vitro, RBC-ND neutralizes the hemolytic activity and cytotoxicity caused by purified α-toxin or complex whole-secreted proteins (wSP) from methicillin-resistant Staphylococcus aureus bacteria. In vivo, RBC-ND confers significant survival benefits for mice intoxicated with α-toxin or wSP in both therapeutic and prevention regimens. Moreover, RBC-ND shows good biocompatibility and biosafety in vivo. Overall, RBC-ND distinguishes itself by inheriting the biological functions of the source cell membrane for bioactivity. The design strategy of RBC-ND can be generalized to other types of cell membranes for broad applications.

Cuprous oxide-demethyleneberberine nanospheres for single near-infrared light-triggered photoresponsive-enhanced enzymatic synergistic antibacterial therapy.

Abstract: In this work, novel cuprous oxide-demethyleneberberine (Cu2O-DMB) nanomaterials are successfully synthesized for photoresponsive-enhanced enzymatic synergistic antibacterial therapy under near-infrared (NIR) irradiation (808 nm). Cu2O-DMB has a spherical morphology with a smaller nanosize and positive ζ potential, can trap bacteria through electrostatic interactions resulting in a targeting function. Cu2O-DMB nanospheres show both oxidase-like and peroxidase-like activities, and serve as a self-cascade platform, which can deplete high concentrations of GSH to produce O2˙- and H2O2, then H2O2 is transformed into ˙OH, without introducing exogenous H2O2. At the same time, Cu2O-DMB nanospheres become photoresponsive, producing 1O2 and having an efficient photothermal conversion effect upon NIR irradiation. The proposed mechanism is that the generated ROS (O2˙-, ˙OH and 1O2) and hyperthermia can have synergetic effects for killing bacteria. Moreover, hyperthermia is not only beneficial for destroying bacteria, but also effectively enhances the efficiency of ˙OH production and accelerates GSH oxidation. Upon NIR irradiation, Cu2O-DMB nanospheres exhibit excellent antibacterial ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) with low cytotoxicity and bare bacterial resistance, destroy the bacterial membrane causing an efflux of proteins and disrupt the bacterial biofilm formation. Animal experiments show that the Cu2O-DMB + NIR group can efficiently treat MRSA infection and promote wound healing. These results suggest that Cu2O-DMB nanospheres are effective materials for combating bacterial infections highly efficiently and to aid the development of photoresponsive enzymatic synergistic antibacterial therapy.

Bamboo-Inspired Structurally Efficient Materials with a Large Continuous Gradient.

Abstract: Because of its light weight and high strength, bamboo is used in many applications around the world. Natural bamboo is built from fiber-reinforced material and exhibits a porous graded architecture that provides its remarkable mechanical performance. This porosity gradient is generated through the unique distribution of densified vascular bundles. Scientists and engineers have been trying to mimic this architecture for a very long time with much of the work focusing on the effect of fiber reinforcement. However, there still lacks quantitative studies on the role of pore gradient design on mechanical properties, in part because the fabrication of bamboo-inspired graded materials is challenging. Here, the steep and continuous porosity gradient through an ingenious cellular design in Moso bamboo is revealed. The effect of gradient design on the mechanical performance is systematically studied by using 3D-printed models. The results show that not only the magnitude of gradient but also its continuity have a significant effect. By introducing a continuous and large gradient, the maximum flexural load and energy absorption capability can be increased by 40% and 110% when comparing to the structure without gradient. These bamboo-inspired cellular architectures can offer efficient solutions for the design of damage tolerant engineering structures.

Immunostimulatory DNA Hydrogel Enhances Protective Efficacy of Nanotoxoids against Bacterial Infection.

Abstract: While vaccines have been highly successful in protecting against various infections, there are still many high-priority pathogens for which there are no clinically approved formulations. To overcome this challenge, researchers have explored the use of nanoparticulate strategies for more effective antigen delivery to the immune system. Along these lines, nanotoxoids are a promising biomimetic platform that leverage cell membrane coating technology to safely deliver otherwise toxic bacterial antigens in their native form for antivirulence vaccination. Here, in order to further boost their immunogenicity, we embed nanotoxoids formulated against staphylococcal α-hemolysin into a DNA-based hydrogel with immunostimulatory CpG motifs. The resulting nanoparticle-hydrogel composite is injectable and improves the in vivo delivery of vaccine antigens while simultaneously stimulating nearby immune cells. This leads to elevated antibody production and stronger antigen-specific cellular immune responses. In murine models of pneumonia and skin infection caused by methicillin-resistant Staphylococcus aureus (MRSA), mice vaccinated with the hybrid vaccine formulation are well protected. This work highlights the benefits of combining nanoparticulate antigen delivery systems with immunostimulatory hydrogels into a single platform, and the approach can be readily generalized to a wide range of infectious diseases. This article is protected by copyright. All rights reserved.

Emerging nanoparticle designs against bacterial infections.

Abstract: The rise of antibiotic resistance has caused the prevention and treatment of bacterial infections to be less effective. Therefore, researchers turn to nanomedicine for novel and effective antibacterial therapeutics. The effort resulted in the first-generation antibacterial nanoparticles featuring the ability to improve drug tolerability, circulation half-life, and efficacy. Toward developing the next-generation antibacterial nanoparticles, researchers have integrated design elements that emphasize physical, broad-spectrum, biomimetic, and antivirulence mechanisms. This review highlights four emerging antibacterial nanoparticle designs: inorganic antibacterial nanoparticles, responsive antibacterial nanocarriers, virulence nanoscavengers, and antivirulence nanovaccines. Examples in each design category are selected and reviewed, and their structure-function relationships are discussed. These emerging designs open the door to nontraditional antibacterial nanomedicines that rely on mechano-bactericidal, function-driven, nature-inspired, or virulence-targeting mechanisms to overcome antibiotic resistance for more effective antibacterial therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Rich structural polymorphism of monolayer C60 from cluster rotation

Abstract: The recent experimental fabrication of monolayer and few-layer C60 polymers paves the way for synthesizing two-dimensional cluster-assembled materials. Compared to atoms with the SO(3) symmetry, clusters as superatoms (e.g., C60) have an additional rotational degree of freedom, greatly enriching the phase spaces of superatom-assembled materials. Using first-principles calculations, we find the energy barriers of cluster rotation in quasi-tetragonal monolayer C60 structures are rather low (about 10 meV/atom). The small rotational energy barriers lead to a series of tetragonal C60 polymorphs with energies that are close to the experimental quasi-tetragonal (expt-qT) phase. Similarly, several dynamically stable quasi-hexagonal monolayer C60 structures are found to have energies within 7 meV/atom above the experimental quasi-hexagonal phase. Our calculations demonstrate photo-excited electron-hole pairs and electrostatic doping of electrons can effectively modulate the relative energies of quasi-tetragonal C60 polymorphs. Particularly, the unstable monolayer expt-qT phase becomes dynamically stable when it is electrostatically doped with electrons. In contrast, the relative energies between different quasi-hexagonal polymorphs are insensitive to electrostatic doping of electrons.

Design Strategies for Cellular Nanosponges as Medical Countermeasures

Abstract: The interest in using therapeutic nanoparticles to bind with harmful molecules or pathogens and subsequently neutralize their bioactivity has grown tremendously. Among various nanomedicine platforms, cell membrane-coated nanoparticles, namely, “cellular nanosponges,” stand out for their broad-spectrum neutralization capability challenging to achieve in traditional countermeasure technologies. Such ability is attributable to their cellular function-based rather than target structure-based working principle. Integrating cellular nanosponges with various synthetic substrates further makes their applications exceptionally versatile and adaptive. This review discusses the latest cellular nanosponge technology focusing on how the structure–function relationship in different designs has led to versatile and potent medical countermeasures. Four design strategies are discussed, including harnessing native cell membrane functions for biological neutralization, functionalizing cell membrane coatings to enhance neutralization capabilities, combining cell membranes and functional cores for multimodal neutralization, and integrating cellular nanosponges with hydrogels for localized applications. Examples in each design strategy are selected, and the discussion is to highlight their structure–function relationships in complex disease settings. The review may inspire additional design strategies for cellular nanosponges and fulfill even broader medical applications.