Bacterial Foreignization Nanosystem Elicits Multi-Phenotypic T Cells for Antitumor Immunity.

T lymphocytes are pivotal targets in clinical cancer immunotherapy; however, tumor cells frequently evade the T-cell attacks by altering the intrinsic immunogenicity manifested as adjuvanticity, antigenicity, and reactogenicity. Here, a bacterial outer membrane vesicle (OMVs)-based nanosystem is presented to elicit robust T-cell responses by reshaping tumor immunogenicity. OMVs are engineered with vesicular stomatitis virus G-protein that facilitates the fusion of OMVs with tumor cells, leading to tumor "foreignization" and adjuvanticity augment.

NAD biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes.

Acute kidney injury (AKI) impairs the energy metabolism and antioxidant capacity of renal proximal tubular cells. Here we show that ultrasound-responsive liposomes integrating thylakoid fragments and encapsulating L-ascorbic acid can restore the energy supply and antioxidant capacity of the tubular cells as well as renal function in animal models of AKI. After intravenous injection, the liposomes preferentially accumulated in the injured kidneys and were internalized by proximal tubular cells.

Fusogenic Lipid Nanovesicles as Multifunctional Immunomodulatory Platforms for Precision Solid Tumor Therapy.

Although immunotherapy demonstrates considerable prospect in overcoming solid tumors, its clinical efficacy is limited by several factors, such as poor tumor immunogenicity, inadequate immune activation, and immunosuppressive tumor microenvironment (TME). To overcome these challenges, a versatile and universal immune modulation platform should be developed, and lipid nanovesicles with membrane fusion capabilities (LNV-Fs) have attracted great attention for this purpose. By mimicking natural membrane fusion processes, LNV-Fs enable the precise presentation of immunogenic components on tumor cell membranes, effectively activating anti-tumor immune surveillance.

Biocompatible nanozyme with dual catalytic activities for high-performance multimodality therapy against glioblastoma.

Nanozymes based on metals have been regarded as a promising candidate in the metabolic reprogramming of low-survival, refractory glioblastoma multiforme (GBM). However, due to size limitations, nanozymes struggle to balance catalytic activity with the ability to cross the blood-brain barrier (BBB), limiting their efficiency in GBM therapy. Herein, we establish a hybrid nanocluster, AuMn NCs, by cross-linking ultrasmall nano-gold (Au) and manganese oxide (MnO), which overcomes the size requirement conflict for integrating catalytic activities, long-period circulation, photothermal effect, glucose consumption, and chemodynamic effect for multimodality treatment against GBM.

Toosendanin promotes prostate cancer cell apoptosis, ferroptosis and M1 polarization via USP39-mediated PLK1 deubiquitination.

Toosendanin (TSN) can inhibit the malignant process of many cancers, and has the potential to be developed as an anti-tumor drug. However, the role and mechanism of TSN in prostate cancer (PCa) progression remain unclear. PCa cells (DU145 and LNCaP) were treated with TSN.

Intratumoral antigen-presenting cell activation by a nanovesicle for the concurrent tertiary lymphoid structure de novo neogenesis.

Tertiary lymphoid structures (TLSs) usually lead to significantly improved clinical benefits in immunotherapy but are rarely observed within native tumors. The current approaches are difficult in effectively inducing TLS formation, let alone fully exploiting its anticancer efficacy. Here, a biomimetic nanovesicle (ADU-S@M1) is constructed to target tumors and then to produce abundant activated antigen-presenting cells (APCs) in situ by polarizing the tumor-associated macrophages toward M1 phenotype and promoting dendritic cell maturation.

AND-Gate Logic Förster Resonance Energy Transfer/Magnetic Resonance Tuning Nanoprobe for Programmable Antitumor Immunity Imaging.

Simultaneous detection of different biomarkers related to the spatiotemporally dynamic immune events is of particular importance for the accurate evaluation of antitumor immune effects. Here, we have developed an AND-gate logic dual resonance energy transfer nanoprobe (named DRET) for dynamic monitoring of programmed CD8 T cell activation and tumor cell apoptosis. Immunotherapy-induced granzyme B secretion from CD8 T cells and the subsequent caspase-3 release from apoptotic tumor cells individually activate one of the tiers of the "AND-gate" logic DRET.

Chemistry-Enabled Intercellular Enzymatic Labeling for Monitoring the Immune Effects of Cytotoxic T Lymphocytes .

Monitoring the effector function of cytotoxic T lymphocytes (CTLs) remains a great challenge. Here, we develop a chemistry-enabled enzymatic labeling approach to evaluate the tumor-specific immune response of CTLs by precisely monitoring the interaction between CTLs and tumor cells. sortase A (SrtA) is linked to the CTL surface through bioconjugate chemistry and then catalyzes the transfer of fluorescent-labeled substrate, 5-Tamra-LPETG, to CTLs.

Nano-Engineering Strategies for Tumor-Specific Therapy.

Nanodelivery systems (NDSs) provide promising prospects for decreasing drug doses, reducing side effects, and improving therapeutic effects. However, the bioapplications of NDSs are still compromised by their fast clearance, indiscriminate biodistribution, and limited tumor accumulation. Hence, engineering modification of NDSs aiming at promoting tumor-specific therapy and avoiding systemic toxicity is usually needed.

Metal-polyphenol "prison" attenuated bacterial outer membrane vesicle for chemodynamics promoted in situ tumor vaccines.

As natural adjuvants, the bacterial outer membrane vesicles (OMV) hold great potential in cancer vaccines. However, the inherent immunotoxicity of OMV and the rarity of tumor-specific antigens seriously hamper the clinical translation of OMV-based cancer vaccines. Herein, metal-phenolic networks (MPNs) are used to attenuate the toxicity of OMV, meanwhile, provide tumor antigens via the chemodynamic effect induced immunogenic cell death (ICD).

Monitoring the Cascade of Tumor-specific Immune Response in vivo via Chemoenzymatic Proximity Labeling.

Monitoring the highly dynamic and complex immune response remains a great challenge owing to the lack of reliable and specific approaches. Here, we develop a strategy to monitor the cascade of tumor immune response through the cooperation of pore-forming alginate gel with chemoenzymatic proximity-labeling. A macroporous gel containing tumor-associated antigens, adjuvants, and pro-inflammatory cytokines is utilized to recruit endogenous DCs and enhance their maturation in vivo.

Biomimetic Nanovesicle with Mitochondria-Synthesized Sonosensitizer and Mitophagy Inhibition for Cancer Sono-Immunotherapy.

Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells.

Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity.

Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity.

In Vivo Imaging for the Visualization of Extracellular Vesicle-Based Tumor Therapy.

Extracellular vesicles (EVs) exhibiting versatile biological functions provide promising prospects as natural therapeutic agents and drug delivery vehicles. For future clinical translation, revealing the fate of EVs in vivo, especially their accumulation at lesion sites, is very important. The continuous development of in vivo imaging technology has made it possible to track the real-time distribution of EVs.

Phytochemical natural killer cells reprogram tumor microenvironment for potent immunotherapy of solid tumors.

Natural killer cells (NKs) hold great promise in cancer treatment, but their application in solid tumors remains a great challenge because current solutions hardly can overcome various difficulties that faced. Herein, we endow NKs with the phytochemical feature for effective immunotherapy of solid tumors. NKs are decorated with natural thylakoid (Tk) membranes through an efficient and convenient membrane fusion strategy.

Phytochemical Engineered Bacterial Outer Membrane Vesicles for Photodynamic Effects Promoted Immunotherapy.

Cancer vaccines are emerging as an attractive modality for tumor immunotherapy. However, their practical application is seriously impeded by the complex fabrication and unsatisfactory outcomes. Herein, we construct bacterial outer membrane vesicles (OMVs)-based cancer vaccine with phytochemical features for photodynamic effects-promoted immunotherapy.

Study on the coupling coordination mechanism of green technology innovation, environmental regulation, and green finance.

Green technology innovation is the basic driving force of green economic development. The compatibility of the composite system composed of green technology innovation, green finance, and environmental regulation is the decisive factor of whether regional economy can achieve sustainable development. Based on the data of regional green technology innovation in China from 2012 to 2020, this paper discusses the coupling coordination mechanism and coupling coordination level among green technology innovation, green finance, and environmental regulation based on entropy method.

Smart Tumor-Cell-Derived Microparticles Provide On-Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy.

Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5-aminolevulinate hydrochloride (HAL) and 3-bromopyruvic acid (3BP) into microparticles collected from X-ray-irradiated tumor cells (X-MP).

Self-Activatable Photo-Extracellular Vesicle for Synergistic Trimodal Anticancer Therapy.

Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self-activatable photo-EV for synergistic trimodal anticancer therapy is reported.

Membrane vesicles nanotheranostic systems: sources, engineering methods, and challenges.

Extracellular vesicles (EVs) are cell secretory native components with long-circulation, good biocompatibility, and physiologic barriers cross ability. EVs derived from different donor cells inherit varying characteristics and functions from their original cells and are favorable to serve as vectors for diagnosing and treating various diseases. However, EVs nanotheranostics are still in their infancy because of their limited accumulation at lesion sites and compromised therapy efficiency.

A self-driven bioinspired nanovehicle by leukocyte membrane-hitchhiking for early detection and treatment of atherosclerosis.

Atherosclerosis, as a silent killer, remains one of the most common causes of human morbidity and mortality worldwide due to the lack of efficient strategy for early detection and targeted therapy. In this work, a self-driven bioinspired nanovehicle is developed, which can accurately manage early atherosclerosis with simultaneously multiple-targeting, dual-modality therapy as well as noninvasive magnetic resonance imaging (MRI). The magnetic nanoclusters (MNCs) with satisfactory superparamagnetism are camouflaged with leukocyte membranes, thus acquiring inherently targeting and transmigrating capabilities to intimal foam cells in early atherosclerotic lesions, which is validated using tailor-made microfluidic devices and transwell assays.

Cell-Membrane-Based Biomimetic Systems with Bioorthogonal Functionalities.

During the past decade, there was a fast development of cell-based biomimetic systems, which are commonly derived from cell membranes, cell vesicles, or living cells. Such systems have unique and inherent bioinspired features originating from their parent biological systems. In particular, they are capable of (i) prolonging blood circulation time, (ii) avoiding immune response, (iii) targeting desired sites, (iv) providing antigens in cancer immunotherapy, and (v) loading and delivering therapeutic or imaging agents.

Biomimetic Microfluidic System for Fast and Specific Detection of Circulating Tumor Cells.

Improving the specific capture efficiency of CTCs, and meanwhile preventing the nonspecific adsorption of surrounding background cells, is the main focus of CTCs detection. Herein, a novel biomimetic microfluidic system was developed by combining the unique benefits of biomimetic nanoparticles and microfluidic techniques. The magnetic nanoclusters were camouflaged with leukocyte membrane fragments and decorated with aptamer SYL3C specific for EpCAM positive tumor cells and then loaded into the microfluidic chip with the help of magnets.

Engineering Magnetosomes for High-Performance Cancer Vaccination.

A novel cancer vaccine is developed by using FeO magnetic nanoclusters (MNCs) as the core and cancer cell membranes decorated with anti-CD205 as the cloak. Because of the superparamagnetism and magnetization of MNCs, it is first achieved for the magnetic retention of vaccine in the lymph nodes with a magnetic resonance imaging (MRI) guide, which opened the time window for antigen uptake by dendritic cells (DCs). Meanwhile, the camouflaged cancer cell membranes serve as a reservoir of various antigens, enabling subsequent multiantigenic response.