<br>用于实时监测炎症小体活动和靶向治疗的纳米报告仪,Advanced Science

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用于实时监测炎症小体活动和靶向治疗的纳米报告仪
Advanced Science ( IF 14.3 ) Pub Date : 2023-01-05 , DOI: 10.1002/advs.202204900
Dipika Nandi _{1,

2} , James Forster ₁ , Anujan Ramesh _{1,

3} , Anh Nguyen ₁ , Hariharan Bharadwaj ₄ , Ashish Kulkarni _{1,

2,

3,

5}

Affiliation

炎症小体激活与多种炎症性疾病相关。然而，现有方法对炎性体激活的时空动力学的理解有限，早期检测相关治疗效果的范围有限。这种限制为开发具有转化前景的生物相容性体内炎症小体监测工具提供了机会。为了实现这一目标，他们报告开发了一对基于脂质的纳米颗粒系统，一种仅由 caspase-1 可激活探针组成的报告纳米颗粒，以及一种将探针与炎症小体抑制药物结合的治疗诊断纳米颗粒。这种生物相容性平台通过防止其调理作用并允许其随着时间的推移持续释放来延长探针在循环中的停留时间。他们的结果证明了报告纳米粒子对 caspase-1 活性的特异性，并提供了体外和体内炎症小体激活的早期监测。此外，双硫仑（一种炎症小体抑制药物）的输送以及使用治疗诊断纳米颗粒的报告探针可以实时跟踪痛风关节炎炎症模型的治疗效果。总之，他们报告了一对无与伦比的炎症体相关报告基因和治疗诊断平台，不仅适合诊断应用，而且还可以实时检测炎症体靶向治疗效率。这些发现建立了两种新颖、灵敏的纳米工具，用于炎症体靶向免疫治疗的非侵入性评估。

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Nanoreporter for Real-Time Monitoring of Inflammasome Activity and Targeted Therapy

Inflammasome activation is associated with a myriad of inflammatory diseases. However, existing methods provides a limited understanding of spatiotemporal kinetics of inflammasome activation, with restricted scope for early detection of associated treatment efficacy. This limitation offers an opportunity for the development of biocompatible in-vivo inflammasome monitoring tools with translational prospects. To achieve this, they report developing a pair of lipid-based nanoparticle systems, a reporter nanoparticle consisting of a caspase-1 activatable probe alone, and a theranostic nanoparticle combining the probe with an inflammasome-inhibiting drug. This biocompatible platform enhances the probe's residence time in circulation by preventing its opsonization and allowing its sustained release over time. Their results demonstrate the specificity of reporter nanoparticles towards caspase-1 activity and provides early-on monitoring of inflammasome activation both in-vitro as well as in-vivo. Additionally, the delivery of disulfiram, an inflammasome-inhibiting drug, along with reporter probe using theranostic nanoparticles enables real-time tracking of treatment efficacy in the gouty-arthritis inflammatory model. In summary, they report an unparalleled pair of the inflammasome-associated reporter and theranostic platforms suited not only for diagnostic applications but can also detect inflammasome-targeted treatment efficiency in real-time. These findings establish two novel, sensitive nanotools for non-invasive evaluation of inflammasome-targeted immunotherapy.

更新日期：2023-01-05

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