Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai, 201203, People's Republic of China.
Key Laboratory of Marine Drugs, Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, People's Republic of China.
J Nanobiotechnology. 2022 Aug 31;20(1):394. doi: 10.1186/s12951-022-01592-6.
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.
上皮间质转化（EMT）是肿瘤细胞异常变化的分化过程，被认为是转移过程的初始和关键步骤。炎症是 EMT 的重要诱导因素，并为阻断 EMT 提供了不可或缺的靶点，然而，缺乏具有突出安全性和疗效的抗炎治疗方法。二甲双胍是一种有前途的抗炎药物，副作用低，但肿瘤的单一抗炎药物治疗可能会产生治疗耐药性、细胞适应性，甚至促进肿瘤发展。具有各种抗炎机制的联合治疗可能是改善二甲双胍治疗效果的有利选择，在这里，我们开发了一种基于二甲双胍和组蛋白去乙酰化酶抑制剂丙泊酚-二十二碳六烯酸的肿瘤靶向混合胶束，以实现抗炎药物的高效治疗效果。雷公藤红素进一步封装在混合胶束中用于原位肿瘤治疗。经过透明质酸（HA）修饰的多功能纳米平台（HAOPTs）可以高效靶向肿瘤，抑制肿瘤细胞 EMT 过程，抑制转移建立，并以协同方式抑制转移性肿瘤的发展。总的来说，这些结果提供了一个概念验证，即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、安全且具有临床转化潜力的方法。
