GOx, glucose oxidase

  • 文章类型: Journal Article
    癌症治疗的主要挑战是如何有效消除原发性肿瘤并充分诱导免疫原性细胞死亡(ICD)以激发强大的免疫反应来控制转移。这里,开发了一种自组装的级联生物反应器,以增强肿瘤渗透和饥饿的协同治疗来改善癌症治疗,化学动力学(CDT)和光热疗法。以葡萄糖氧化酶(GOx)为模板合成超小FeS-GOx纳米点,紫杉醇(PTX)通过疏水作用诱导形成自组装FeS-GOx@PTX(FGP)。在肿瘤部位积累后,FGP分解为较小的FeS-GOx,以增强肿瘤的深层渗透。GOx维持高的酶活性以在氧的辅助下催化葡萄糖以产生过氧化氢(H2O2)作为饥饿疗法。涉及再生H2O2的Fenton反应进而产生更多的羟基自由基以增强CDT。跟随808nm的近红外激光,通过联合治疗,FGP在体外和体内显示出显著的肿瘤抑制。随之而来的钙网织蛋白暴露增加了ICD并促进了树突状细胞的成熟。结合抗CTLA4检查点封锁,由于细胞毒性T淋巴细胞的肿瘤内浸润增强,FGP可以绝对消除原发性肿瘤并积极抑制远处肿瘤。我们的工作提出了一种有希望的原发性肿瘤和转移抑制策略。
    Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP) via hydrophobic interaction. After accumulated at tumor sites, FGP disassembles to smaller FeS-GOx for enhanced deep tumor penetration. GOx maintains high enzymatic activity to catalyze glucose with assistant of oxygen to generate hydrogen peroxide (H2O2) as starvation therapy. Fenton reaction involving the regenerated H2O2 in turn produced more hydroxyl radicals for enhanced CDT. Following near-infrared laser at 808 nm, FGPs displayed pronounced tumor inhibition in vitro and in vivo by the combination therapy. The consequent increased exposure to calreticulin amplified ICD and promoted dendritic cells maturation. In combination with anti-CTLA4 checkpoint blockade, FGP can absolutely eliminate primary tumor and avidly inhibit distant tumors due to the enhanced intratumoral infiltration of cytotoxic T lymphocytes. Our work presents a promising strategy for primary tumor and metastasis inhibition.
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  • 文章类型: Journal Article
    最近的传染病爆发,如COVID-19和埃博拉病毒,强调了快速准确诊断以启动治疗和遏制传播的必要性。成功的诊断策略关键取决于生物采样和及时分析的效率。然而,当前的诊断技术是侵入性/侵入性的,并且由于需要专业设备和训练有素的人员而成为严重的瓶颈。此外,集中式测试设施难以接近,旅行的要求可能会增加疾病传播。自我管理,现场护理(PoC)微针诊断设备可以为这些问题提供可行的解决方案。这些微型针阵列可以以微创方式检测皮肤中/来自皮肤的生物标志物以提供(近)实时诊断。很少有微针装置专门用于传染病诊断,尽管类似的技术在其他领域已经很成熟,并且通常适用于传染病的诊断。这些包括用于生物流体提取的微针,微针传感器和分析物捕获微针,或其组合。可以从血液和皮肤间质液进行分析物采样/检测。这些技术正处于传染病诊断的早期发展阶段,还有很大的发展空间。在这次审查中,我们讨论了这些微针技术在传染病诊断中的实用性和未来前景。
    Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.
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  • 文章类型: Journal Article
    随着生物治疗的发展,生物大分子药物最近获得了极大的关注,特别是在药物开发领域由于复杂的体内功能。在过去的几年里,已经开发了各种各样的生物大分子药物给药策略,以克服成药的困难,例如,不稳定,容易受到生理障碍的限制。应用新型递送系统递送生物大分子药物通常可以延长半衰期,增加生物利用度,或提高患者的依从性,大大提高了生物大分子药物的疗效和临床应用潜力。在这次审查中,总结了近年来关于高分子药物在癌症治疗中的药物递送策略的研究,主要是借鉴过去五年的发展。
    With the development of biotherapy, biomacromolecular drugs have gained tremendous attention recently, especially in drug development field due to the sophisticated functions in vivo. Over the past few years, a motley variety of drug delivery strategies have been developed for biomacromolecular drugs to overcome the difficulties in the druggability, e.g., the instability and easily restricted by physiologic barriers. The application of novel delivery systems to deliver biomacromolecular drugs can usually prolong the half-life, increase the bioavailability, or improve patient compliance, which greatly improves the efficacy and potentiality for clinical use of biomacromolecular drugs. In this review, recent studies regarding the drug delivery strategies for macromolecular drugs in cancer therapy are summarized, mainly drawing on the development over the last five years.
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