Surface modification of lipid nanoparticles for gene therapy.

Gene therapies have the potential to target and effectively treat a variety of diseases including cancer as well as genetic, neurological, and autoimmune disorders. Although we have made significant advances in identifying non-viral strategies to deliver genetic cargo, certain limitations remain. In general, gene delivery is challenging for several reasons including the instabilities of nucleic acids to enzymatic and chemical degradation and the presence of restrictive biological barriers such as cell, endosomal and nuclear membranes. The emergence of lipid nanoparticles (LNPs) helped overcome many of these challenges. Despite its success, further optimization is required for LNPs to yield efficient gene delivery to extrahepatic tissues, as LNPs favor accumulation in the liver after systemic administration. In this mini-review, we provide an overview of current preclinical approaches in that LNP surface modification was leveraged for cell and tissue targeting by conjugating aptamers, antibodies, and peptides among others. In addition to their cell uptake and efficiency-enhancing effects, we outline the (dis-)advantages of the different targeting moieties and commonly used conjugation strategies.

Programmed immobilization of living cells using independent click pairs.

Therapeutic devices incorporating living cells or tissues have been intensively investigated for applications in tissue engineering and regenerative medicine. Because many biological processes are governed by spatially dependent signals, programmable immobilization of materials is crucial for manipulating multiple types of cells. In this study, click chemistry substrates were introduced onto the surfaces of cells and cover glass, and the cells were fixed on the cover glass via covalent bonds for selective cell deposition. Azide group (Az)-labeled living cells were prepared by metabolic labeling with azido sugars. Following the introduction of Az, TCO (trans-cyclooctene) was metabolically labeled into the living cells by reacting with TCO-DBCO (dibenzocyclooctyne). Az and TCO in the cells were detected using DBCO-FAM (fluorescein)and tetrazine-Cy3, respectively. The mixture of Az-labeled green fluorescent protein HeLa cells and TCO-labeled red fluorescent protein HeLa cells was reacted in a culture dish in which three different cover glasses, DBCO-, tetrazine-, or methyl-coated, were added. Az- or TCO-labeled cells could be immobilized in a functional group-dependent manner. Next, tetrazine-labeled cells were incubated on TCO- or Az-labeled cell layers instead of cover glass. Functional group-dependent immobilization was also achieved in the cell layer. Introducing substrates for the click reaction could achieve cell-selective immobilization on different patterned glass surfaces, as well as cell-cell immobilization.

Mussel and Cobweb Inspired High Areal Capacity SPAN Electrode.

Lithium-sulfur batteries (LSBs) with superior energy density are among the most promising candidates for next-generation energy storage techniques. Sulfurized polyacrylonitrile (SPAN) exhibits competitive advantages in terms of cycle stability, rate performance as well as cost. However, the preparation of high-loading SPAN electrodes is still challenging. Herein, inspired by mussel and cobweb, a high-loading SPAN electrode is enabled by the combination of polydopamine (PDA) coating and a bimodal distributed single-wall carbon nanotubes (SWCNT) slurry dispersed in polyvinylpyrrolidone (PVP), their synergistic effect not only constructs effective electron percolating networks within the electrode but also make high active material (AM) ratio possible. High areal capacity PDA@SPAN electrode (18.40 mAh cm-2 in the initial cycle) with negligible specific capacity attenuation as the mass loading increasement is realized through the facile slurry casting process. The dynamic N─H…O hydrogen bond is formed between PDA and PVP and the electrode integrity during charge/discharge is greatly strengthened. The battery with an areal AM loading of 7.16 mg cm-2 (5.16 mAh cm-2) retains 92.0% of capacity in 80 cycles and 87.18% in 160 cycles, and it also shows stable cycle performances even with a high loading of 19.79 mg cm-2 and lean electrolyte (3.28 µL mg-1).

Stabilized Li-Rich Layered Oxide Cathode by a Spontaneously Formed Yb and Oxygen-Vacancy Rich Layer on the Surface.

Li-rich layered oxides (LLOs) are among the most promising cathode materials with high theoretical specific capacity (>250 mAh g-1 ). However, capacity decay and voltage hysteresis due tostructural degradation during cycling impede the commercial application of LLOs. Surface engineering and element doping are two methods widely applied tomitigate the structural degradation. Here, it is found that trace amount lanthanide element Yb doping can spontaneously form a surficial Yb-rich layer with high density of oxygen vacancy on the LLO-0.3% Yb (Li1.2 Mn0.54 Co0.13-x Ybx Ni0.13 O2 where x = 0.003) cathodes, which mitigating lattice oxygen loss and the non-preferred layered-to-spinel-to-rock salt tri-phase transition. Meanwhile, there are also some Yb ions doped into the lattice of LLO, which enhance the binding energy with oxygen and stabilize the lattice in grain interior during cycling. The dual effects of Yb doping greatly mitigate the structure degradation during cycling, and facilitate fast diffusion of lithium ions. As a result, the LLO-0.3% Yb sample achieves significantly improved cycling stability, with a capacity retention of 84.69% after 100 cycles at 0.2 C and 84.3% after 200 cycles at 1 C. These finding shighlight the promising rare element doping strategy that can have both surface engineering and doping effects in preparing LLO cathodes with high stability.

Nanopatterning Induced Si Doping in Amorphous Ga2O3 for Enhanced Electrical Properties and Ultra-Fast Photodetection.

Ga2O3 has emerged as a promising material for the wide-bandgap industry aiming at devices beyond the limits of conventional silicon. Amorphous Ga2O3 is widely being used for flexible electronics, but suffers from very high resistivity. Conventional methods of doping like ion implantation require high temperatures post-processing, thereby limiting their use. Herein, an unconventional method of doping Ga2O3 films with Si, thereby enhancing its electrical properties, is reported. Ion-beam sputtering (500 eV Ar+) is utilized to nanopattern SiO2-coated Si substrate leaving the topmost part rich in elemental Si. This helps in enhancing the carrier conduction by increasing n-type doping of the subsequently coated 5 nm amorphous Ga2O3 films, corroborated by room-temperature resistivity measurement and valence band spectra, respectively, while the nanopatterns formed help in better light management. Finally, as proof of concept, metal-semiconductor-metal (MSM) photoconductor devices fabricated on doped, rippled films show superior properties with responsivity increasing from 6 to 433 mA W-1 while having fast detection speeds of 861 µs/710 µs (rise/fall time) as opposed to non-rippled devices (377 ms/392 ms). The results demonstrate a facile, cost-effective, and large-area method to dope amorphous Ga2O3 films in a bottom-up approach which may be employed for increasing the electrical conductivity of other amorphous oxide semiconductors as well.

Surface Engineering of Natural Killer Cells with CD44-targeting Ligands for Augmented Cancer Immunotherapy.

Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.

Exploiting the Photo-Physical Properties of Metal Halide Perovskite Nanocrystals for Bioimaging.

Perovskite nanomaterials have recently been exploited for bioimaging applications due to their unique photo-physical properties, including high absorbance, good photostability, narrow emissions, and nonlinear optical properties. These attributes outperform conventional fluorescent materials such as organic dyes and metal chalcogenide quantum dots and endow them with the potential to reshape a wide array of bioimaging modalities. Yet, their full potential necessitates a deep grasp of their structure-attribute relationship and strategies for enhancing water stability through surface engineering for meeting the stringent and unique requirements of each individual imaging modality. This review delves into this evolving frontier, highlighting how their distinctive photo-physical properties can be leveraged and optimized for various bioimaging modalities, including visible light imaging, near-infrared imaging, and super-resolution imaging.

Close Proximity of Cholesterol Anchors in Membrane Induces the Dissociation of Amphiphilic DNA Strand from Membrane Surface.

Dynamic DNA nanotechnology is appealing for membrane surface engineering due to their versatility and programmability. To modulate the dynamic interactions between the DNA functional units immobilized on membrane surface, membrane-anchored DNA functional units often come into close proximity each other due to DNA base pairing, which also leads to the close contact of the hydrophobic anchors in membrane. However, whether the close contact of hydrophobic anchors induces the dissociation of amphiphilic DNA structures from membrane surface is not concerned. Herein, we utilized cholesterol-labeled single-stranded DNA (ssDNA) as a simplified amphiphilic DNA structure to investigate the stability of membrane anchored DNA strands upon the closely contact of cholesterol anchors. The close contact of cholesterol-labeled ssDNA molecules driven by toe-hold mediated strand displacement reaction leads to approximately 41 % membrane anchored ssDNA dissociation from membrane surface, indicating the proximal cholesterol anchors in membrane could reduce the anchoring stability of cholesterol-modified DNA strands. This work enhances our understanding of the interactions between amphiphilic DNA and membranes, and provides valuable insights for the design of future DNA constructs intended for applications involving dynamic DNA reactions on membrane surface.

Surface Engineering of the Mechanical Properties of Molecular Crystals via an Atomistic Model for Computing the Facet Stress Response of Solids.

Dynamic molecular crystals are an emerging class of crystalline materials that can respond to mechanical stress by dissipating internal strain in a number of ways. Given the serendipitous nature of the discovery of such crystals, progress in the field requires advances in computational methods for the accurate and high-throughput computation of the nanomechanical properties of crystals on specific facets which are exposed to mechanical stress. Here, we develop and apply a new atomistic model for computing the surface elastic moduli of crystals on any set of facets of interest using dispersion-corrected density functional theory (DFT-D) methods. The model was benchmarked against a total of 24 reported nanoindentation measurements from a diverse set of molecular crystals and was found to be generally reliable. Using only the experimental crystal structure of the dietary supplement, L-aspartic acid, the model was subsequently applied under blind test conditions, to correctly predict the growth morphology, facet and nanomechanical properties of L-aspartic acid to within the accuracy of the measured elastic stiffness of the crystal, 24.53±0.56 GPa. This work paves the way for the computational design and experimental realization of other functional molecular crystals with tailor-made mechanical properties.

Janus Structure Construction of Polyester-Cotton Fabrics for Achieving Excellent Moisture, Moisture-Permeability, and Antibacterial Capability.

Integration of hydrophobic and antibacterial functionalities into polyester-cotton blended (PTCO) textiles has attracted more attention but remains a challenge. Here, a Janus fabric with antibacterial effect, hydrophobicity, and enhanced moisture-permeability is fabricated using a "mist polymerization" approach. The PET fibers in the PTCO fabric are amino-functionalized through ammonolysis reactions of PET molecules with HDA, and mist treatments of poly lauryl methacrylate (PLMA) and poly(DMC-co-MA) (PDM) are applied on the two side surfaces of the PTCO-HDA fabric, respectively. The resulting Janus fabric exhibits an antibacterial rate of 99.9% against both E. coli and S. aureus, along with a hydrophobic property on its single side (PTCO-HDA@PLMA). Additionally, the establishment of a surface-free energy gradient across the fabric confers superior moisture-permeability to the Janus fabric, offering advantages in preserving textile comfort. Moreover, this approach does not significantly compromise the original fabric properties, such as mechanical strength, moisture permeability, and fabric softness. The proposed method offers a straightforward and scalable strategy for textile finishing, demonstrating great potential in expanding the application scope of PTCO fabrics, and it may hold a pivotal role in diverse applications, notably encompassing home textiles, wound dressings, and high-performance sportswear.

Improving Triethylamine-Sensing Performance of WO3 Nanoplates through In Situ Heterojunction Construction.

Surface engineering techniques can be used to develop high-performance gas sensing materials and advance the development of sensors. In this study, we improved the gas sensing performance of two-dimensional (2D) WO3 nanoplates by combining surface Zn modification and the in situ formation of ZnWO4/WO3 heterojunctions. Introducing Zn atoms by surface modification can reconstruct the atomic surface of 2D WO3 nanoplates, creating additional active sites. This allowed for the preparation of various types of ZnWO4/WO3 heterojunctions on the surface of the WO3 nanoplates, which improved the selectivity and sensitivity to the target gas triethylamine. The sensor exhibited good gas sensing performance for triethylamine even at low operating temperatures and strongly resisted humidity changes. The ZnWO4/WO3 material we prepared demonstrated a nearly threefold improvement in the triethylamine (TEA) response, with a gas sensing responsivity of 40.75 for 10 ppm of TEA at 250 °C. The sensor based on ZnWO4/WO3 has a limit of detection (LOD) for TEA of 200 ppb in practical measurements (its theoretical LOD is even as low as 31 ppb). The method of growing ZnWO4 on the surface of WO3 nanoplates using surface modification techniques to form surface heterojunctions differs from ordinary composites. The results suggest that the in situ construction of surface heterojunctions using surface engineering strategies, such as in situ modifying, is a practical approach to enhance the gas sensing properties and resistance to the humidity changes of metal oxide materials.

Gas Vesicle-Blood Interactions Enhance Ultrasound Imaging Contrast.

Gas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as systemically injectable nanomaterials have been hindered by a lack of understanding of GVs' interactions with blood components, which can significantly impact in vivo behavior. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface we can alter these interactions and thereby modify GVs' in vivo performance. These results provide critical insights for the development of GVs as agents for nanomedicine.

Triple Ligand Engineered Gold Nanoclusters with Enhanced Fluorescence and Device Compatibility for Efficient Electroluminescence Light-Emitting Diodes.

Gold nanoclusters (Au NCs) are potential emitters for electroluminescent light-emitting diodes (EL-LEDs) but restricted by the limited photoluminescence quantum yield (PLQY) and poor device compatibility. Herein, triple ligand engineered Au NCs enable the fabrication of Au NC-based LEDs with improved EL efficiency. Rigidified triple ligand shells greatly reduce the nonradiative transition and thus increase the PLQY of Au NCs from 2.1 to 73.4%. Most importantly, this strategy significantly improves the compatibility between Au NCs and charge transport materials in EL-LED fabrication. As a result, the EL-LEDs reach a maximum brightness of 1104 cd/m2 and an external quantum efficiency of 5.1%, which is the highest recorded for any reported Au NC-based EL-LEDs.

Metal-Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy.

Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi-step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole-cell cancer vaccine by cloaking cancer cells with lipopolysaccharide-decorated manganese(II)-phenolic networks (MnTA nanocloaks) to evoke tumor-specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti-programmed cell death ligand 1 (anti-PD-L1) antibodies-mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell-based nanobiohybrid system for enhanced cancer immunotherapy.

Proximity-Enhanced Functional Imaging Analysis of Engineered Tumors.

Functional imaging (FI) techniques have revolutionized tumor imaging by providing information on specific tumor functions, such as glycometabolism. However, tumor cells lack unique molecular characteristics at the molecular level and metabolic pathways, resulting in limited metabolic differences compared to normal cells and increased background signals from FI. To address this limitation, we developed a novel imaging technique termed proximity-enhanced functional imaging (PEFI) for accurate visualization of tumors. By using "two adjacent chemically labeled glycoproteins" as output signals, we significantly enhance the metabolic differences between tumor and normal cells by PEFI, thereby reducing the background signals for analysis and improving the accuracy of tumor functional imaging. Our results demonstrate that PEFI can accurately identify tumors at the cellular, tissue, and animal level, and has potential value in clinical identification and analysis of tumor cells and tissues, as well as in the guidance of clinical tumor resection surgery.

Cell Surface Engineering by Phase-Separated Coacervates for Antibody Display and Targeted Cancer Cell Therapy.

Cell therapies such as CAR-T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase-separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc-Lys-Gly-Dopa-OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody-embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody-dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer-targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy.

Pt Nanoparticle Assisted Homogeneous Surface Engineering of Polymer-Based Bulk-Heterojunction Photocathodes for Efficient Charge Extraction and Catalytic Hydrogen Evolution.

To fabricate a high-efficiency bulk-heterojunction (BHJ)-based photocathode, introducing suitable interfacial modification layer(s) is a crucial strategy. Surface engineering is especially important for achieving high-performance photocathodes because the photoelectrochemical (PEC) reactions at the photocathode/electrolyte interface are the rate-limiting process. Despite its importance, the influence of interfacial layer morphology regulation on PEC activity has attracted insufficient attention. In this work, RuO2 , with excellent conductivity, capacity and catalytic properties, is utilized as an interfacial layer to modify the BHJ layer. However, the homogeneous coverage of hydrophilic RuO2 on the hydrophobic BHJ surface is challenging. To address this issue, a Pt nanoparticle-assisted homogeneous RuO2 layer deposition method is developed and successfully applied to several BHJ-based photocathodes, achieving superior PEC performance compared to those prepared by conventional interface engineering strategies. Among them, the fluorine-doped tin oxide (FTO)/J71:N2200(Pt)/RuO2 photocathode generates the best photocurrent density of -9.0 mA cm-2 at 0 V with an onset potential of up to 1.0 V under AM1.5 irradiation.

P-Block Metal-Based Electrocatalysts for Nitrogen Reduction to Ammonia: A Minireview.

Electrochemical nitrogen reduction reaction (NRR) to ammonia (NH3 ) using renewable electricity provides a promising approach towards carbon neutral. What's more, it has been regarded as the most promising alternative to the traditional Haber-Bosch route in current context of developing sustainable technologies. The development of a class of highly efficient electrocatalysts with high selectivity and stability is the key to electrochemical NRR. Among them, P-block metal-based electrocatalysts have significant application potential in NRR for which possessing a strong interaction with the N 2p orbitals. Thus, it offers a good selectivity for NRR to NH3 . The density of state (DOS) near the Fermi level is concentrated for the P-block metal-based catalysts, indicating the ability of P-block metal as active sites for N2 adsorption and activation by donating p electrons. In this work, we systematically review the recent progress of P-block metal-based electrocatalysts for electrochemical NRR. The effect of P-block metal-based electrocatalysts on the NRR activity, selectivity and stability are discussed. Specifically, the catalyst design, the nature of the active sites of electrocatalysts and some strategies for boosting NRR performance, the reaction mechanism, and the impact of operating conditions are unveiled. Finally, some challenges and outlooks using P-block metal-based electrocatalysts are proposed.

Role of MoOx Surficial Modification in Enhancing the OER Performance of Ru-Pyrochlore.

Pyrochlore ruthenate (Y2 Ru2 O7-δ ) is highlighted as a promising oxygen evolution reaction (OER) catalyst for water splitting in polymer electrolyte membrane electrolyzers. However, an efficient electronic modulation strategy for Y2 Ru2 O7-δ is required to overcome its electrochemical inertness. Herein, a surface manipulation strategy involving implanting MoOx moieties on nano Y2 Ru2 O7-δ (Mo-YRO) using wet chemical peroxone method is demonstrated. In contrast to electronic structure regulation by intramolecular charge transfer (i.e., substitutional strategies), the heterogeneous Mo-O-Ru micro-interfaces facilitate efficient intermolecular electron transfer from [RuO6 ] to MoOx . This eliminates the bandgap by inducing Ru 4d delocalization and band alignment rearrangement. The MoOx modifiers also alleviate distortion of [RuO6 ] by shortening Ru-O bond and enlarging Ru-O-Ru bond angle. This electronic and geometric structure tailoring enhances the OER performance, showing a small overpotential of 240 mV at 10 mA cm-2 . Moreover, the electron-accepting MoOx moieties provide more electronegative surfaces, which serve as a protective "fence" to inhibit the dissolution of metal ions, thereby stabilizing the electrochemical activity. This study offers fresh insights into the design of new-based pyrochlore electrocatalysts, and also highlights the versatility of surface engineering as a way of optimizing electronic structure and catalytic performance of other related materials.

Applications of Bacteria Decorated with Synthetic DNA Constructs.

The advent of DNA nanotechnology has revolutionized the way DNA has been perceived. Rather than considering it as the genetic material alone, DNA has emerged as a versatile synthetic scaffold that can be used to create a variety of molecular architectures. Modifying such self-assembled structures with bio-molecular recognition elements has further expanded the scope of DNA nanotechnology, opening up avenues for using synthetic DNA assemblies to sense or regulate biological molecules. Recent advancements in this field have lead to the creation of DNA structures that can be used to modify bacterial cell surfaces and endow the bacteria with new properties. This mini-review focuses on the ways by which synthetic modification of bacterial cell surfaces with DNA constructs can expand the natural functions of bacteria, enabling their potential use in various fields such as material engineering, bio-sensing, and therapy. The challenges and prospects for future advancements in this field are also discussed.