Multi-Metallic Nanosheets Reshaping Immunosuppressive Tumor Microenvironment through Augmenting cGAS-STING Innate Activation and Adaptive Immune Responses for Cancer Immunotherapy.

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME.

A Guanidinobenzol-Rich Polymer Overcoming Cascade Delivery Barriers for CRISPR-Cas9 Genome Editing.

The efficient cytosolic delivery of the CRISPR-Cas9 machinery remains a challenge for genome editing. Herein, we performed ligand screening and identified a guanidinobenzol-rich polymer to overcome the cascade delivery barriers of CRISPR-Cas9 ribonucleoproteins (RNPs) for genome editing. RNPs were stably loaded into the polymeric nanoparticles (PGBA NPs) by their inherent affinity.

Engineered Bio-Based Hydrogels for Cancer Immunotherapy.

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy and severe immune-related side effects are frequently encountered, especially in solid tumors. Hydrogels, a class of versatile materials featuring well-hydrated structures widely used in biomedicine, offer a promising platform for encapsulating and releasing small molecule drugs, biomacromolecules, and cells in a controlled manner.

Manganese-Enriched Zinc Peroxide Functional Nanoparticles for Potentiating Cancer Immunotherapy.

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy by inducing the immunogenic death (ICD) of cancer cells and activating the stimulator of the interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tumor tissue and in situ generate •OH for the ICD effect.

Tumor Microenvironment-Responsive Nanoparticles Amplifying STING Signaling Pathway for Cancer Immunotherapy.

Insufficient activation of the stimulator of interferon genes (STING) signaling pathway and profoundly immunosuppressive microenvironment largely limits the effect of cancer immunotherapy. Herein, tumor microenvironment (TME)-responsive nanoparticles (PMM NPs) are exploited that simultaneously harness STING and Toll-like receptor 4 (TLR4) to augment STING activation via TLR4-mediated nuclear factor-kappa B signaling pathway stimulation, leading to the increased secretion of type I interferons (i.e.

Imaging Guided Endogenic H -Augmented Electrochemo-Sonodynamic Domino Co-therapy of Tumor in Vivo.

Precise and on-demand release of sufficient hydrogen (H ) to tumor sites remains a key challenge for emerging H -oncotherapy, and little is known about the physiological effects of "abundant" H on complex tumor microenvironments (TME). Here, a highly efficient and cost-effective imaging-guided/-assessed H -therapy of tumors based on a joint electrochemo-sonodynamic treatment (H -EC/SD co-therapy) with strong "domino effect" triggered by endogenous H generation at tumor sites is reported to speedily eliminate tumor tissue (≤80 mm ) within 1 day. Adequate H is controllably generated in tumor sites through mild electrochemistry in vivo due to acidic TME by using clinical acupuncture Fe needles as electrodes.

Engineered Nanoprobes for Immune Activation Monitoring.

The activation of the immune system is critical for cancer immunotherapy and treatments of inflammatory diseases. Non-invasive visualization of immunoactivation is designed to monitor the dynamic nature of the immune response and facilitate the assessment of therapeutic outcomes, which, however, remains challenging. Conventional imaging modalities, such as positron emission tomography, computed tomography, , were utilized for imaging immune-related biomarkers.

Optoplasmonic Modulation of Cell Metabolic State Promotes Rapid Cell Differentiation.

Cell differentiation plays a vital role in mediating organ formation and tissue repair and regeneration. Although rapid and effective methods to stimulate cell differentiation for clinical purposes are highly desired, it remains a great challenge in the medical fields. Herein, a highly effective and conceptual optical method was developed based on a plasmonic chip platform (made of 2D AuNPs nanomembranes).

Photoactivated Bacteriorhodopsin/SiN Nanopore-Based Biological Nanofluidic Generator with Single-Protein Sensitivity.

Nanofluidics is an emerging hot field that explores the unusual behaviors of ions/molecules transporting through nanoscale channels, which possesses a broad application prospect. However, in situ probing bioactivity of functional proteins on a single-molecule level by a nanofluidic device has not been reported, and it is still a big challenge in the field. Herein, we reported a biological nanofluidic device with a single-protein sensitivity, based on natural proton-pumping protein, bacteriorhodopsin (bR), and a single SiNx nanopore.

Label-Free Analysis of Cell Membrane Proteins via Evanescent Field Excited Surface-Enhanced Raman Scattering.

Challenges in studying the structures and functions of cell membrane proteins lie in their lipophilicity, which makes them hard to be stabilized, crystallized, and expressed by . Herein, we propose an evanescent field excited surface-enhanced Raman scattering (EF-SERS) strategy for label-free analysis of membrane proteins . Extracted cell membranes tightly wrapped the metal nanoparticles by an extruder, which ensures the SERS signals of the membrane proteins precisely benefit from the localized surface plasmons (LSPs).

Wet-Chemical Electro-Plasmonic Modulation of Metasurfaced Cell-Electrode Interfaces for Effective and Selective Entropic Killing of Cancer Cells.

Surface plasmons (SPs) of metallic nanostructures excited by optical ways have been extensively utilized for versatile sensing, biomedical, catalysis, and energy conversion applications. Nevertheless, utilizing the electrically excited plasmonic field (effect) of metallic nanostructures (and electrodes) in wet-chemical conditions, for catalytic and energy conversion, especially for potential biological and biomedical applications, is still poorly studied. Herein, we report a conceptual and biocompatible wet-chemical platform and approach to utilize the electrically excited plasmonic field (effect) of metasurfaced plasmonic electrodes (without light irradiation) for cell fate regulation on electrode surfaces.

Plasmon-enhanced unidirectional charge transfer for efficient solar water oxidation.

Precise modulation and nano-engineering of photoelectrochemical (PEC) materials, with high-speed charge separation efficiency and broad spectral response, are of significant importance in improving the PEC catalytic activities. Herein, by rational design of material structures, 3D-coaxial plasmonic hetero-nanostructures (carbon cloth@TiO2@SrTiO3-Au, CC@TiO2@SrTiO3-Au) are tactfully fabricated, which exhibit superior solar energy conversion efficiency in PEC water splitting with a current density reaching up to 23.56 mA cm-2 (1.

Label-Free Single-Particle Surface-Enhanced Raman Spectroscopy Detection of Phosphatidylserine Externalization on Cell Membranes with Multifunctional Micron-Nano Composite Probes.

Monitoring externalization of phosphatidylserine (PS) and gaining insights into molecular events of cell membrane damage are significant for programmed cell death studies. Herein, by encapsulating zeolitic imidazole frameworks-8 with plasmonic gold nanoparticles to form micron-nano composites and using them as a single-particle surface-enhanced Raman spectroscopy (SERS) substrate, we succeeded in real-time discriminating and monitoring the externalization of PS on cell membranes during electrostimulus-induced apoptosis. The micron-nano composite probe provides rich "hot spots" and robust anchoring capacity for cell membranes, achieving the capture and label-free single-particle SERS detection of the externalized PS.

Plasmonic SERS Au Nanosunflowers for Sensitive and Label-Free Diagnosis of DNA Base Damage in Stimulus-Induced Cell Apoptosis.

Molecular diagnosis and accurate damage analysis of complex genomic DNAs in tumor cells are crucial to the theranostics of cancers but still a huge challenge. Herein, by designed preparation of a uniform plasmonic sunflower-like assembly gold (Au) nanostructure that is capable of efficient DNA capture and providing high-density gap-plasmon "hot spots" for adequate surface-enhanced Raman spectroscopy (SERS) enhancement, we succeeded in sensitive and reliable label-free SERS detection of DNA damage in electrostimulus-induced apoptotic cancer cells at the DNA base level for the first time. The SERS results showed that the external electrostimulus (at 1.

Tumor Microenvironment-Activated Degradable Multifunctional Nanoreactor for Synergistic Cancer Therapy and Glucose SERS Feedback.

Integration of disease diagnosis and therapy in vivo by nanotechnology is a challenge in the design of multifunctional nanocarriers. Herein, we report an intelligent and degradable nanoreactor, an assembly of the 4-mercaptobenzonitrile-decorated silver nanoparticles (AgNPs@MBN) and the glucose oxidase (GOx)-loaded metal-organic-framework (ZIF-8@GOx), which can be activated by tumor microenvironment to start the catalytic cascade-enhanced chemo-starvation synergistic therapy and simultaneous self-sense of cellular glucose level. Under the mild acidic microenvironment of tumor, the nanoreactor will collapse to release GOx that triggers a catalytic cascade reaction in vivo, depleting glucose, etching AgNPs@MBN, and producing toxic HO, Ag, and Zn ions, all of which work together to inhibit tumor growth.

Fast Activation and Tracing of Caspase-3 Involved Cell Apoptosis by Combined Electrostimulation and Smart Signal-Amplified SERS Nanoprobes.

Caspase-3 is considered as one of the key proteases that can spontaneously regulate the life activities of cells, and its activation (usually is a slow process) will execute the apoptosis process of cells. Rapid activation of caspase-3 on demand in living-cells is therefore highly desired toward precise cancer therapy but it is still a key challenge. Herein, we applied electrostimulus (ES) to achieve fast activation of caspase-3 and trigger cell apoptosis, and developed a smart magnetic-plasmonic assembly nanoprobes (A-nanoprobes) to real-time trace cellular caspase-3 activation at the single cell level.