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    Home > Active Ingredient News > Antitumor Therapy > Advanced Materials breakthrough!

    Advanced Materials breakthrough!

    • Last Update: 2021-06-22
    • Source: Internet
    • Author: User
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    Editor’s note iNature is China’s largest academic official account.
    It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
    The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
    .

    iNature specifically targets the blood vessels of glioblastoma multiforme (GBM) and actively enhances the permeability of the brain blood tumor barrier (BBTB) are two extremely difficult challenges for the development of effective therapies for GBM
    .

    On June 9, 2021, Southeast University Yang Fang and Gu Ning jointly published a study titled "Sphingosine 1-Phosphate Liposomes for Targeted Nitric Oxide Delivery to Mediate Anticancer Effects against Brain Glioma Tumors" in Advanced Materials (IF=27.
    40).
    The paper, the study describes a liposomal drug delivery system (S1P/JS-K/Lipo) that delivers nitric oxide (NO) prodrug JS-K, using sphingosine 1-phosphate (S1P) signaling The molecule acts as an active targeting lipid ligand and acts on GBM tumors
    .

    The results showed that S1P/JS-K/Lipo actively penetrated BBTB with the help of caveolin-1 mediated endocytosis, and proved that the system specifically interacts with S1P receptors (S1PRs) that are highly expressed on GBM cells
    .

    Non-destructive ultrasound imaging in the GBM mouse model is also used to observe the micro-NO bubbles produced by JS-K, which are catalyzed by glutathione S-transferase (GST) residing in GBM cells
    .

    Given that these NO bubbles strongly promote GBM cell death in the body, the S1PR targeted liposome delivery system has successfully achieved BBTB penetration and tumor-targeted delivery of a complex multi-component drug regimen, which represents a target for GBM and other characteristic cancers A promising method of treatment
    .

    Glioblastoma multiforme (GBM) is a WHO grade IV astrocytoma, accounting for the majority (60-70%) of all gliomas
    .

    It is an aggressive primary tumor of the central nervous system (CNS), with a five-year survival rate of less than 6%
    .

    The current standard treatment of GBM is the use of gefitinib, erlotinib and temozolomide chemotherapy drugs
    .

    However, due to low targeting efficiency and P-glycoprotein (P-gp) efflux pump-related drug resistance, none of these (or related modified therapies) have shown statistically significant results relative to placebo for GBM treatment.
    Steady improvement
    .

    The main challenges that limit effective drug therapy for GBM include: 1) the lack of proven targets that are vulnerable to effective intervention; 2) the low level of accumulation of treatment at the tumor site due to the physical and biochemical functions of the blood-brain tumor barrier (BBTB)
    .

    This BBTB penetration problem is particularly challenging because uneven penetration and drug outflow in the BBTB microenvironment around active cancer cells can severely hinder the efficacy of drugs on primary brain tumors
    .

    According to reports, nitric oxide (NO) plays an important role in tumor biology
    .

    The administration of high concentrations of NO has been shown to cause nitrosative stress and subsequently induce apoptosis of cancer cells
    .

    Although this therapy has shown great potential in cancer treatment, to date, most NO delivery agents have short half-lives, low bioavailability, and poor tumor targeting, which limit the efficacy in vivo
    .

    To overcome these challenges, the study describes a liposomal drug delivery system (S1P/JS-K/Lipo) that delivers nitric oxide (NO) prodrug JS-K using sphingosine 1-phosphate ( S1P) signaling molecules act as active targeting lipid ligands for GBM tumors
    .

    Clinical reports show that the S1P concentration in GBM is significantly increased; in view of the specific high affinity between the biologically active lipid S1P signal molecule and the transmembrane G protein-coupled receptor family of the sphingosine 1-phosphate receptor (S1PR), These signaling molecules have the potential to deliver targeted NO therapeutics to GBM tumor cells
    .

    Based on these extensive data, the study selected the biologically active S1P molecule as the BBTB receptor target for the proof-of-concept work of establishing an in-situ GBM targeted drug delivery platform
    .

    In addition, the study selected JS-K NO prodrug as a therapeutic diagnostic agent to use high concentrations of in situ NO production to induce anticancer effects and provide ultrasound imaging to monitor target participation
    .

    By combining the liposomal drug delivery platform with the S1P molecule, this study proved that S1P/JS-K/Lipo can produce a specific response to BBTB endothelial cells and improve the targeting of glioma cells in the Transwell in vitro system Efficiency
    .

    In addition, this study clarified that the BBTB traversal mechanism of S1P/JS-K/Lipo is mediated by Cavelion-1 enhanced endocytosis and P-gp efflux inhibition
    .

    In conclusion, given that these NO bubbles strongly promote GBM cell death in the body, the S1PR targeted liposome delivery system has successfully achieved BBTB penetration and tumor-targeted delivery of a complex multi-component drug regimen, which represents an effective strategy for GBM and other characteristic cancers.
    A promising approach to targeted therapy
    .

    Reference message: https://onlinelibrary.
    wiley.
    com/doi/10.
    1002/adma.
    202101701
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