Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors.
Artificial exosomes mediated spatiotemporal-resolved and targeted delivery of epigenetic inhibitors.
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人工外泌体介导表观遗传抑制剂的时空解析和靶向递送。
DOI：
10.1186/s12951-021-01107-9
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发表时间：
2021-11-17
影响因子：
10.2
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Li H;Li S;Lin Y;Chen S;Yang L;Huang X;Wang H;Yu X;Zhang L
恶性肿瘤通常与表观遗传失调有关，如组蛋白去乙酰化酶（HDAC）的过度表达，因此HDAC已成为癌症的治疗靶点。组蛋白去乙酰化酶抑制剂已被批准用于临床治疗血液癌症。但其溶解度低、循环寿命短、细胞毒性大等缺点限制了其在实体瘤中的应用。用介孔二氧化硅（SUC）修饰的上转换纳米颗粒（UC）用于负载HDACI、辛二酰苯胺异羟肟酸（SAHA），并进一步用M1巨噬细胞衍生的外泌体膜（EMS）包裹。EMS的特点是大小和组成。我们还分析了EMS诱导的表观遗传调控。此外，我们评估EMS全身给药后的生物分布和体内肿瘤抑制。这种新型的时空分辨给药系统EMS对SAHA具有很高的载药效率。EMS可被肺癌细胞摄取并导致有效的表观遗传抑制。我们首次发现M1-EM上的整合素α4β1对EMS归巢至肿瘤组织至关重要。在荷瘤小鼠体内，EMS表现出时空分辨特性，并促进药物在肿瘤内的蓄积，从而诱导出优越的上级抗肿瘤作用。这种新型的时空分辨纳米粒子可以用作肺癌治疗的诊断平台。在线版本包含补充材料，可通过10.1186/s12951-021-01107-9获得。
Malignant tumor is usually associated with epigenetic dysregulation, such as overexpression of histone deacetylase (HDAC), thus HDAC has emerged as a therapeutic target for cancer. Histone deacetylase inhibitor has been approved for clinical use to treat hematological cancers. However, the low solubility, short circulation lifetime, and high cytotoxicity partially limited their applications in solid tumor. The upconversion nanoparticles (UC) modified with mesoporous silica (SUC) was used to load an HDACI, suberoylanilide hydroxamic acid (SAHA), and further camouflaged with M1 macrophage-derived exosome membranes (EMS). EMS was characterized in size and compositions. We also analyzed the epigenetic regulation induced by EMS. Furthermore, we evaluate the biodistribution and in vivo tumor inhibition after the systemic administration of EMS. This novel style spatiotemporal-resolved drug delivery system, EMS showed a high loading efficiency of SAHA. EMS could be taken up by lung cancer cells and lead to efficient epigenetic inhibition. We found that the integrin α4β1 on M1-EM, was crucial for the homing of EMS to tumor tissues for the first time. In tumor-bearing mice, EMS showed spatiotemporal-resolved properties and facilitated the drug accumulation in the tumors, which induced superior anti-tumor effects. This novel style of spatiotemporal-resolved nanoparticles can be used as a theranostic platform for lung cancer therapy. The online version contains supplementary material available at 10.1186/s12951-021-01107-9.
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