Polycatechol-Derived Mesoporous Polydopamine Nanoparticles for Combined ROS Scavenging and Gene Interference Therapy in Inflammatory Bowel Disease.
Polycatechol-Derived Mesoporous Polydopamine Nanoparticles for Combined ROS Scavenging and Gene Interference Therapy in Inflammatory Bowel Disease.
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DOI：
10.1021/acsami.1c25180
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发表时间：
2022-04
影响因子：
9.5
通讯作者：
Liucan Wang;Zhenqiang Wang;Yiyang Pan;Shuaishuai Chen;Xin Fan;Xiaolong Li;Guo-qing Chen;Yuanhang Ma;Yujiao Cai;Jixi Zhang;Hua Yang;W. Xiao;Min Yu
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作者：
Liucan Wang;Zhenqiang Wang;Yiyang Pan;Shuaishuai Chen;Xin Fan;Xiaolong Li;Guo-qing Chen;Yuanhang Ma;Yujiao Cai;Jixi Zhang;Hua Yang;W. Xiao;Min Yu
得益于纳米技术的发展，基因干扰与活性氧（ROS）清除的联合治疗有望在炎症性肠病（IBD）治疗中具有巨大的潜力。然而，迫切需要通过基因载体的界面修饰实现不同治疗模块的功能整合，以实现安全有效的治疗。在此，我们提出了一个儿茶酚化学介导的核壳纳米平台，用于在葡聚糖硫酸钠（DSS）诱导的结肠炎模型中进行ROS清除介导的氧化应激缓解和sirna介导的基因干扰。该纳米平台采用表面修饰胺的介孔聚多巴胺纳米粒子（MPDA NPs）作为装载TNF-α-siRNA的多孔核心（31% wt %），并发挥抗氧化功能，而pda诱导的磷酸钙（CaP）涂层作为ph敏感的保护壳，以防止siRNA过早释放。CaP层在弱酸性亚细胞条件下（溶酶体）降解；因此，儿茶酚和阳离子在MPDA暴露表面的协同整合导致了高效的溶酶体逃逸。随后，MPDA提供电子的能力导致了有效的ROS清除，并通过充分的细胞质基因传递有效降低（40.5%）肿瘤坏死因子-α (TNF-α)，从而在体外和体内产生协同抗炎症治疗效果。这项工作建立了通过ROS清除和基因干扰对IBD进行协同治疗的第一个范例。
Benefiting from the evolution of nanotechnology, the combination therapy by gene interference and reactive oxygen species (ROS) scavenging are expected, which holds great potential in inflammatory bowel disease (IBD) therapy. However, the functional integration of different therapeutic modules through interface modification of gene vectors for safe and efficient treatment is urgently needed. Herein, we present a catechol chemistry-mediated core-shell nanoplatform for ROS scavenging-mediated oxidative stress alleviation and siRNA-mediated gene interference in a dextran sulfate sodium (DSS)-induced colitis model. The nanoplatform is constructed by employing mesoporous polydopamine nanoparticles (MPDA NPs) with surface modification of amines as the porous core for TNF-α-siRNA loading (31 wt %) and exerts an antioxidant function, while PDA-induced biomineralization of the calcium phosphate (CaP) coating is used as the pH-sensitive protective shell to prevent siRNA from premature release. The CaP layer degraded under weakly acidic subcellular conditions (lysosomes); thus, the synergistic integration of catechol and cation moieties on the exposed surface of MPDA resulted in an efficient lysosomal escape. Subsequently, effective ROS scavenging caused by the electron-donating ability of MPDA and efficient knocking down (40.5%) of tumor necrosis factor-α (TNF-α) via sufficient cytosolic gene delivery resulted in a synergistic anti-inflammation therapeutic effect both in vitro and in vivo. This work establishes the first paradigm of synergistic therapy in IBD by ROS scavenging and gene interference.