Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment.
Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment.
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基于二甲双胍和组蛋白脱乙酰酶抑制剂的抗炎纳米平台用于上皮间质转化抑制和转移性肿瘤治疗
DOI：
10.1186/s12951-022-01592-6
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发表时间：
2022-08-31
影响因子：
10.2
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Jiang, Tianze;Xie, Laozhi;Zhou, Songlei;Liu, Yipu;Huang, Yukun;Mei, Ni;Ma, Fenfen;Gong, Jingru;Gao, Xiaoling;Chen, Jun
关键词：
上皮-间质转化（Epithelial-mesenchymal transition， EMT）是肿瘤细胞发生异常变化的一种分化过程，被认为是转移过程的初始和重要过程。炎症是EMT的重要诱导剂，是阻断EMT不可缺少的靶点，但缺乏安全性和有效性突出的抗炎治疗方法。二甲双胍是一种很有前景的抗炎药，副作用小，但单用抗炎药治疗肿瘤可能产生治疗耐药性、细胞适应甚至促进肿瘤发展。多种抗炎机制的联合治疗是提高二甲双胍治疗效果的良好选择，本研究基于二甲双胍和组蛋白去乙酰化酶抑制剂异丙酚-二十二碳六烯酸开发了肿瘤靶向杂交胶束，以提高抗炎药物的治疗效果。雷公藤甲素进一步封装在杂交胶束中用于原位肿瘤治疗。经透明质酸修饰的最终多功能纳米平台（HAOPTs）能够有效靶向肿瘤，抑制肿瘤细胞EMT过程，抑制转移建立，协同抑制转移瘤的发展。总的来说，这些结果证明了肿瘤靶向抗炎纳米平台可以为EMT抑制和转移性肿瘤治疗提供一种有效、安全的临床转化方法。在线版本包含补充材料，可在10.1186/s12951-022-01592-6获得。
Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy. The online version contains supplementary material available at 10.1186/s12951-022-01592-6.
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作者：
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