CD22-targeted glyco-engineered natural killer cells offer a further treatment option for B-cell acute lymphoblastic leukemia.

Not available.

Amplification of anticancer efficacy by co-delivery of doxorubicin and lonidamine with extracellular vesicles.

Chemotherapy is commonly used for the treatment of lung cancer, but strong side effects and low treatment efficacy limit its clinical application. Here, extracellular vesicles (EVs) as natural drug delivery carriers were used to load conventional anticancer drug doxorubicin (DOX) and a chemosensitizer lonidamine (LND). Two types of EVs with different sizes (16k EVs and 120k EVs) were prepared using different centrifugation forces. We found that co-delivery of DOX and LND with both EVs enhanced the cytotoxicity and reduced the dose of the anticancer drug significantly in vitro. Effective delivery of anti-cancer drugs to cancer cells was achieved by direct fusion of EVs with the plasma membrane of cancer cells. On the other hand, DOX and LND inhibited cancer cell proliferation by increasing DNA damage, suppressing ATP production, and accelerating ROS generation synergistically. DOX and LND loaded EVs were also applied to the mouse lung cancer model and exhibited significant anticancer activity. In vivo study showed that smaller EVs exhibited higher anticancer efficiency. In conclusion, the co-delivery of the anticancer drug and the chemosensitizer with EVs may have potential clinical applications for cancer therapy.

Equipping Natural Killer Cells with Cetuximab through Metabolic Glycoengineering and Bioorthogonal Reaction for Targeted Treatment of KRAS Mutant Colorectal Cancer.

While Cetuximab can be used to treat KRAS wild-type colon cancer cells by targeting EGFR and inhibiting the activation of downstream signaling pathways, it exhibits little therapeutic effect on KRAS mutant colon cancer cells. Natural killer (NK) cells are a class of powerful immune cells with anticancer activities. However, NK cells typically lack inherent tumor targeting abilities. Here, a new method is established to bestow NK-92 cells with tumor targeting abilities by installing cetuximab on the cell surface. Through metabolic glycoengineering, azide groups were introduced onto the surface of NK-92 cells. Bioorthogonal strain promoted the azide-alkyne cycloaddition click reaction of engineered NK-92 cells with alkyne modified cetuximab functionalized NK cells with the antibody. The resulting NK-92 cells were significantly more effective than the parent NK-92 cells in protecting against tumor development in a KRAS mutant mouse tumor model resistant to cetuximab treatment. Thus, NK cell functionalization with antibodies enabled by metabolic glycoengineering is a promising strategy to enhance anticancer immune therapy.

Glycoengineering of Natural Killer Cells with CD22 Ligands for Enhanced Anticancer Immunotherapy.

Adoptive transfer of immune cells is being actively pursued for cancer treatment. Natural killer (NK) cells, a class of cytotoxic immune cells, generally lack inherent selectivities toward cancer. To bestow tumor-targeting abilities and enhance anticancer efficacy, a new strategy is established to glycoengineer NK cells. Carbohydrate-based ligands for CD22, a marker for B cell lymphoma, are introduced onto NK cells through either metabolic engineering or glyco-polymer insertion. Such NK cells exhibited greatly enhanced cytotoxicities toward CD22+ lymphoma cells in a CD22-dependent manner. Importantly, both CD22+ lymphoma cell lines and primary lymphoma cells from human cancer patients can be effectively killed by the engineered NK cells. Furthermore, glycoengineered NK cells provided significant protection to tumor-bearing mice. Thus, NK cell glycoengineering is an exciting new approach for cancer treatment complementing the current immune cell genetic engineering strategy.

A hydrogel biosensor for high selective and sensitive detection of amyloid-beta oligomers.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive and memory impairment. It is the most common neurological disease that causes dementia. Soluble amyloid-beta oligomers (AßO) in blood or cerebrospinal fluid (CSF) are the pathogenic biomarker correlated with AD. METHODS: A simple electrochemical biosensor using graphene oxide/gold nanoparticles (GNPs) hydrogel electrode was developed in this study. Thiolated cellular prion protein (PrPC) peptide probe was immobilized on GNPs of the hydrogel electrode to construct an AßO biosensor. Electrochemical impedance spectroscopy was utilized for AßO analysis. RESULTS: The specific binding between AßO and PrPC probes on the hydrogel electrode resulted in an increase in the electron-transfer resistance. The biosensor showed high specificity and sensitivity for AßO detection. It could selectively differentiate AßO from amyloid-beta (Aß) monomers or fibrils. Meanwhile, it was highly sensitive to detect as low as 0.1 pM AßO in artificial CSF or blood plasma. The linear range for AßO detection is from 0.1 pM to 10 nM. CONCLUSION: This biosensor could be used as a cost-effective tool for early diagnosis of AD due to its high electrochemical performance and bionic structure.

A Nile blue based infrared fluorescent probe: imaging tumors that over-express cyclooxygenase-2.

The first Golgi-localized cyclooxygenase-2 (COX-2)-specific near-infrared (NIR) fluorescent probe, Niblue-C6-IMC, able to detect cancer cells, was designed. Importantly, Niblue-C6-IMC preferentially labeled the tumors in a mouse tumor model with deep tissue penetration capacity. It may be a promising molecular tool for guiding tumor resection during surgery.

Lighting up fluoride ions in cellular mitochondria using a highly selective and sensitive fluorescent probe.

We report a highly selective and sensitive fluorescent probe () for detecting fluoride ions, for the first time, lighting up the fluoride ions in mitochondria with a strong green fluorescence. could be easily prepared as fluoride paper test strips to detect fluoride ions in aqueous solutions with a detection limit as low as 19 ppb.