N-Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression.

Primary cilia are microtubule-based organelles that function as cellular antennae to address multiple metabolic and extracellular cues. The past decade has seen significant advances in understanding the pro-tumorigenic role of N-methyladenosine (mA) modification in tumorigenesis. Nevertheless, whether mA modification modulates the cilia dynamics during cancer progression remains unclear.

Zinc Coordination Lipid Nanoparticles Co-Delivering Calcium Peroxide and Chelating STING agonist for Enhanced Cancer Metalloimmunotherapy.

Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within the tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO) nanoparticles and the STING agonist diABZI-2, which is termed A-CaO-Zn-LNP.

Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy.

Oxygen Self-Supplied Perfluorocarbon-Modified Micelles for Enhanced Cancer Photodynamic Therapy and Ferroptosis.

Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127.

Small Molecule-Inducible and Photoactivatable Cellular RNA N1-Methyladenosine Editing.

N1-methyladenosine (mA) modification is one of the most prevalent epigenetic modifications on RNA. Given the vital role of mA modification in RNA processing such as splicing, stability and translation, developing a precise and controllable mA editing tool is pivotal for in-depth investigating the biological functions of mA. In this study, we developed an abscisic acid (ABA)-inducible and reversible mA demethylation tool (termed AI-dmA), which targets specific transcripts by combining the chemical proximity-induction techniques with the CRISPR/dCas13b system and ALKBH3.

N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA.

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA mA accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that mA triggered the generation of glutathione (GSH) via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential.

METTL3 promotes cellular senescence of colorectal cancer via modulation of CDKN2B transcription and mRNA stability.

Cellular senescence plays a critical role in cancer development, but the underlying mechanisms remain poorly understood. Our recent study uncovered that replicative senescent colorectal cancer (CRC) cells exhibit increased levels of mRNA N6-methyladenosine (mA) and methyltransferase METTL3. Knockdown of METTL3 can restore the senescence-associated secretory phenotype (SASP) of CRC cells.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method.

MoS-Based Memristor: Robust Resistive Switching Behavior and Reliable Biological Synapse Emulation.

Memristors are recognized as crucial devices for future nonvolatile memory and artificial intelligence. Due to their typical neuron-synapse-like metal-insulator-metal(MIM) sandwich structure, they are widely used to simulate biological synapses and have great potential in advancing biological synapse simulation. However, the high switch voltage and inferior stability of the memristor restrict the broader application to the emulation of the biological synapse.

Isothermal Amplification-Based Detection of Single-Base RNA N6-Methyladenosine.

N6-methyladenosine (mA) has recently gained much attention due to its diverse biological functions. Currently, the commonly used detection methods for locus-specific mA marks are complicated to operate, it is difficult to quantify the methylation level, and they have high false-positive levels. Here, we report a new method for locus-specific mA detection based on the methylate-sensitive endonuclease activity of MazF and the simultaneous amplification and testing (SAT) method, termed "mA-MazF-SAT".

Orally-Delivered, Cytokine-Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease.

The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages.

Anti-Tumor Immunity Induced by a Ternary Membrane System Derived From Cancer Cells, Dendritic Cells, and Bacteria.

Cancer vaccines generally are limited by insufficient tumor-specific cellular immunogenicity. Herein, a potent "ABC" ternary membrane-derived vaccine system blended from antigen-presenting mature dendritic cell membranes ("A"), bacterial E. coli cytoplasmic membranes ("B"), and cancer cell membranes ("C") is developed using a block-copolymer micelle-enabled approach.

N6-Methyladenosine Promotes Translation of VEGFA to Accelerate Angiogenesis in Lung Cancer.

Unlabelled: Angiogenesis is hijacked by cancer to support tumor growth. RNA modifications such as N6-methyladenosine (m6A) can regulate several aspects of cancer, including angiogenesis. Here, we find that m6A triggers angiogenesis in lung cancer by upregulating VEGFA, a central regulator of neovasculature and blood vessel growth.

Metal coordination micelles for anti-cancer treatment by gene-editing and phototherapy.

CRISPR-Cas9 is a central focus of the emerging field of gene editing and photodynamic therapy (PDT) is a clinical-stage ablation modality combining photosensitizers with light irradiation. But metal coordination biomaterials for the applications of both have rarely been investigated. Herein, Chlorin-e6 (Ce6) Manganese (Mn) coordination micelles loaded with Cas9, termed Ce6-Mn-Cas9, were developed for augmented combination anti-cancer treatment.

Rolling circle extension-assisted loop-mediated isothermal amplification (Rol-LAMP) method for locus-specific and visible detection of RNA N6-methyladenosine.

N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic mRNAs. Currently available detection methods for locus-specific m6A marks rely on RT-qPCR, radioactive methods, or high-throughput sequencing. Here, we develop a non-qPCR, ultrasensitive, isothermal, and naked-eye visible method for m6A detection based on rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP), named m6A-Rol-LAMP, to verify putative m6A sites in transcripts obtained from the high-throughput data.

N-methyladenosine modification in cancer biology: Current status and future perspectives.

Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N-methyladenosine (mA), which is dynamically regulated by writers, erasers and readers, has been found as a reversible modification in tRNA, mRNA, rRNA and long non-coding RNA (lncRNA). mA modification has impacts on the RNA processing, structure and functions of targets.

RNA m A methylation in cancer.

N -methyladenosine (m A) is one of the most abundant internal modifications in eukaryotic messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). It is a reversible and dynamic RNA modification that has been observed in both internal coding segments and untranslated regions. Studies indicate that m A modifications play important roles in translation, RNA splicing, export, degradation and ncRNA processing control.

Manganese Coordination Micelles That Activate Stimulator of Interferon Genes and Capture In Situ Tumor Antigens for Cancer Metalloimmunotherapy.

Cancer immunotherapy holds great promise but is generally limited by insufficient induction of anticancer immune responses. Here, a metal micellar nanovaccine is developed by the self-assembly of manganese (Mn), a stimulator of interferon genes (STING) agonist (ABZI) and naphthalocyanine (ONc) coordinated nanoparticles (ONc-Mn-A) in maleimide-modified Pluronic F127 (malF127) micelles. Owing to synergy between Mn and ABZI, the nanovaccine, termed ONc-Mn-A-malF127, elevates levels of interferon-β (IFNβ) by 324- and 8-fold in vivo, compared to use of Mn or ABZI alone.

Colistin Crosslinked Gemcitabine Micelles to Eliminate Tumor Drug Resistance Caused by Intratumoral Microorganisms.

In the tumor microenvironment, there exist microorganisms that metabolize anticancer drugs, leading to chemotherapy failure. To solve this problem, herein, we develop antibiotic and anticancer drug co-delivery micelles, termed colistin crosslinked gemcitabine micelle (CCGM). A self-immolative linker enables colistin and gemcitabine to be released on demand without affecting their antibacterial and anticancer effects.

RNA mA methylation regulates glycolysis of cancer cells through modulating ATP5D.

Studies on biological functions of RNA modifications such as -methyladenosine (mA) in mRNA have sprung up in recent years, while the roles of -methyladenosine (mA) in cancer progression remain largely unknown. We find mA demethylase ALKBH3 can regulate the glycolysis of cancer cells via a demethylation activity dependent manner. Specifically, sequencing and functional studies confirm that ATP5D, one of the most important subunit of adenosine 5'-triphosphate synthase, is involved in mA demethylase ALKBH3-regulated glycolysis of cancer cells.

A novel inhibitor of -methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities.

-methyladenosine (mA) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified mA demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay.

RNA mA methylation regulates dissemination of cancer cells by modulating expression and membrane localization of β-catenin.

N6-methyladenosine (mA) methylation, which is modified by the METTL3/METTL14 complex, is a dominant internal modification in mammalian RNA and tightly linked to cancer progression. Here we reveal that METTL3-promoted cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) are associated with expression and membrane localization of β-catenin (encoded by CTNNB1), as opposed to Wnt signaling activation in various types of cancer cells, including cervical, lung, and liver cancer. Specifically, METTL3 regulates the transcription, mRNA decay, translation, and subcellular localization of β-catenin.