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Plasmid DNA ionisable lipid nanoparticles as non-inert carriers and potent immune activators for cancer immunotherapy
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2024-03-29 , DOI: 10.1016/j.jconrel.2024.03.018
Yue Qin , Nadia Rouatbi , Julie Tzu-Wen Wang , Rafal Baker , James Spicer , Adam A. Walters , Khuloud T. Al-Jamal

Immunotherapy is currently a standard of care in the treatment of many malignancies. However, predictable side effects caused by systemic administration of highly immunostimulatory molecules have been a serious concern within this field. Intratumoural expression or silencing of immunogenic and immunoinhibitory molecules using nucleic acid-based approaches such as plasmid DNA (pDNA) and small interfering RNA (siRNA), respectively, could represent a next generation of cancer immunotherapy. Here, we employed lipid nanoparticles (LNPs) to deliver either non-specific pDNA and siRNA, or constructs targeting two prominent immunotherapeutic targets OX40L and indoleamine 2,3-dioxygenase-1 (IDO), to tumours .

中文翻译:

质粒 DNA 可电离脂质纳米粒子作为非惰性载体和用于癌症免疫治疗的有效免疫激活剂

免疫疗法目前是治疗许多恶性肿瘤的标准治疗方法。然而,高度免疫刺激分子的全身给药引起的可预测的副作用一直是该领域的一个严重问题。分别使用基于核酸的方法(例如质粒 DNA (pDNA) 和小干扰 RNA (siRNA))在肿瘤内表达或沉默免疫原性和免疫抑制分子,可能代表下一代癌症免疫疗法。在这里,我们使用脂质纳米颗粒 (LNP) 将非特异性 pDNA 和 siRNA 或针对两个重要免疫治疗靶点 OX40L 和吲哚胺 2,3-双加氧酶-1 (IDO) 的构建体递送至肿瘤。
更新日期:2024-03-29
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