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    Home > Active Ingredient News > Antitumor Therapy > Experts comment on Nat Nanotech| Gu Zhen's team develops anti-tumor patch, in situ catalyzed reaction to produce anti-cancer drugs

    Experts comment on Nat Nanotech| Gu Zhen's team develops anti-tumor patch, in situ catalyzed reaction to produce anti-cancer drugs

    • Last Update: 2021-05-21
    • Source: Internet
    • Author: User
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    Comments | Shi Jianlin (Academician of the Chinese Academy of Sciences) Editor | Xi In recent years, research on transition metal-mediated bio-orthogonal catalytic reactions has been in the ascendant, through which biomolecules can be selectively labeled or bioactive substances can be synthesized in situ.

    Transition metal catalysts that perform bioorthogonal catalysis mainly include complexes and nanoparticles.

    However, due to the unpredictable toxicity, lack of targeting and limited stability of transition metal complexes, most of the current research is still limited to the cellular level.

    For example, how to remove transition metal catalysts after treatment, potential metal toxicity, immunogenicity, and non-specific deposition causing catalytic reactions at non-target sites, and other issues have hindered the clinical application of bioorthogonal catalysis.

    On May 10, 2021, Professor Gu Zhen’s team from the School of Pharmacy of Zhejiang University and the Run Run Run Run Run Run Run Hospital reported their latest research technology-"Bioorthogonal Catalytic Patch" online on Nature Nanotechnology (pictured) 1) For the treatment of tumors.

    The research team used polyvinyl alcohol (PVA) as the matrix of the microneedle patch, mixed with titanium dioxide nanosheets deposited by palladium nanoparticles, and prepared a bio-orthogonal catalytic device that can increase efficiency, reduce toxicity, and is easy to use (Figure 2) Anti-cancer drugs can be produced in situ through a catalytic reaction where the patch is used.

    Palladium nanoparticles can catalyze the "decagging reaction" of N-(allyloxycarbonyl)-protected drug molecules (prodrugs), so that prodrugs with low toxicity can quickly become drugs with anti-tumor effects.

    Titanium dioxide nanosheets are rich in hydroxyl groups, which can be used as a carrier for palladium nanoparticle catalysts, and can be evenly dispersed in the PVA matrix, giving the microneedles enough strength to penetrate the tumor in a minimally invasive manner.

    Using a mouse melanoma model, the research team confirmed that the prodrug molecule of the chemotherapy drug doxorubicin injected into the body through systemic administration can be activated in situ in the tumor pre-inserted with the microneedle patch to produce the doxorubicin molecule and Enriched, significantly inhibit tumor growth.

    Using this patch device with bio-orthogonal catalysis ability, local activation of the prodrug can not only increase the dose of the drug, but also reduce the toxic and side effects of the original drug on healthy organs and tissues.

    In particular, this kind of microneedle still has sufficient mechanical strength in the hydrated state, which facilitates the removal of the entire device after use, and avoids residual transition metal in the body or cause inflammation and other reactions.

    Figure 1.
    Schematic diagram of microneedle patch-mediated bioorthogonal catalysis.

    Figure 2.
    Bio-orthogonal catalytic patch loaded with titanium dioxide nanosheets deposited with palladium nanoparticles.

    The physical image of the microneedle patch loaded with transition metal catalyst (a), the scanning electron microscope image (b), and the scanning electron microscope image of the microneedle section (c).

    Gu Zhen's team has developed a blood glucose-responsive "smart insulin patch", proposed a new concept of "prescribe the right medicine" closed-circuit transdermal drug delivery system, and systematically expanded the biomedical creation of microneedles.

    In this study, they used the microneedle patch as the carrier of the bioorthogonal catalyst to achieve the orthogonal activation of local in situ anticancer prodrugs at the tumor site in a simple and effective way.

    While allowing the intake of high-dose prodrugs, it only catalyzes the synthesis of therapeutically effective drugs at the tumor site, reducing the toxic and side effects of the original drug on normal organs and tissues, and the toxic catalyst in the needle can be combined with the microneedle patch Remove from the body.

    This research developed a simple and effective bio-orthogonal catalytic device by combining the microneedle patch and transition metal catalyst, which provides a new idea for realizing unnatural catalytic reactions in vivo.
    It is expected that the invention of this innovative device can derive more Many drugs that increase efficacy and reduce toxicity and related diagnosis and treatment technologies.

    Original link: Expert comment Shi Jianlin Academician of the Chinese Academy of Sciences (Shanghai Institute of Ceramics, Chinese Academy of Sciences) Bioorthogonal catalysis refers to the use of unnatural transition metals The catalyst carries out the labeling of biomolecules or the synthesis of substances in a complex biological environment.

    A very promising application in this field is to activate prodrug molecules in situ in a way that does not depend on physiological conditions.

    However, the complex biological environment and the toxicity of transition metals make the application of bioorthogonal catalysis in living organisms challenging.

    In the work published this time in Nature Nanotechnology, in order to overcome the difficulties of using bio-orthogonal catalysis in vivo, Gu Zhen’s team combined the microneedle patch with the transition metal catalyst.
    Through optimized component design, it can not only be used in tumors.
    Local in situ activation of anti-cancer prodrugs taken by systemic administration can easily remove transition metals after treatment to avoid residual transition metals in the body.

    This strategy reduces the difficulty and cost of unnatural catalytic reactions in organisms, and provides a new platform for the development of prodrug therapy technology.

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