包硅镍钴合金纳米颗粒通过核磁共振成像及抑制炎症小体激活实现肿瘤诊疗一体

We previously reported that self-assembled Ni-Co alloy nanoparticles can achieve diagnosis and treatment through magnetic resonance imaging (MRI) and inducing the autophagy-dependent cell death. To further improve the biocompatibility of Ni-Coalloy, silica was introduced to encapsulate it. Capsulate silica improved water solubility and biocompatibility of the material without attenuating theMRI effects of it. Interesting, the NiCo@SiO2 nanoparticles can inhibit the activation of NLRP3, NLRC4 and AIM2 inflammasome which was different from the reported engneering nanoparticles which were always found to active the inflammasome. We also found the anti-inflammatory effects of NiCo@SiO2 was attenuated by autophagy inhibitor treatment. So we plan to explore the mechnism of NiCo@SiO2 inhibition the inflammasome activation through autophagy pathway, and provide a new method for inhibiting inflammasome activation. As the activation of inflammasome was considered to participate in the occurrence and development of tumor, we plan to test the MRI ability of NiCo@SiO2 in animal models, and at the same time, to verif that the NiCo@SiO2 inhibit tumor development and metastasis by inhibiting the activation of inflammasome.Finally, we hope to provide a new way of thinking about the application of nano-materials in the diagnosis and treatment of cancer

申请人前期工作显示，自组装镍钴合金纳米颗粒可用于核磁共振成像，以及诱导自噬促进细胞死亡。为了提高镍钴合金造影剂的生物相容性，我们对其表面进行了包硅修饰，修饰后的镍钴合金不仅具有很好的造影能力，而且提高了稳定性和生物相容性。不同于已经报道的工程纳米颗粒通常导致炎症小体激活，包硅镍钴合金可以显著抑制NLRP3，NLRC4和AIM2炎症小体激活，抑制自噬则会减轻其抑炎效果。所以我们拟开展镍钴合金通过调控自噬发挥抗炎效果的机制探究，为抑制炎症小体激活提供新的方法。由于炎症小体的激活在肿瘤的发生发展过程中起着非常重要的作用，我们将在动物水平验证包硅镍钴合金增强肿瘤核磁共振成像效果的同时，通过抑制炎症小体的激活来抑制肿瘤发展和转移的能力，为纳米材料应用于肿瘤的诊断和治疗提供一种全新的思路。

炎性小体的激活与多种疾病有关，目前已经有多种不同结构、化学组成的无机纳米材料被报道会导致炎性小体过度激活。与其他无机纳米材料的报道形成鲜明对比的是，我们发现镍钴合金纳米晶体(NiCo NCs)显著抑制NLRP3、NLRC4和AIM2炎性小体的激活。利用转录组测序进行机制研究，发现NiCo NCs通过下调lncRNA Neat1来破坏炎性小体组装过程。最后，我们发现NiCo NCs通过抑制验证小体的激活，在急性腹膜炎小鼠模型中抑制中性粒细胞募集，以及在结肠炎小鼠模型中缓解症状，并且NiCo具有良好的生物相容性。我们的工作为将含镍/钴的纳米材料用于巨噬细胞介导的炎症相关疾病的治疗提供了科学依据。