CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering , University of Science and Technology of China , Hefei 230026 , Anhui China.
Innovation Center of NanoMedicine (iCONM) , Kawasaki Institute of Industrial Promotion , 3-25-14 Tonomachi , Kawasaki-ku, Kawasaki 210-0821 , Japan.
ACS Nano. 2019 Feb 26;13(2):2357-2369. doi: 10.1021/acsnano.8b09082. Epub 2019 Feb 1.
Therapeutic nanoreactors are of increasing interest in precise cancer therapy, which have been explored to in situ produce therapeutic compounds from inert prodrugs or intrinsic molecules at the target sites. However, engineering a nanoreactor with tumor activable cascade reactions for efficient cooperative cancer therapy remains a great challenge. Herein, we demonstrate a polymersome nanoreactor with tumor acidity-responsive membrane permeability to activate cascade reactions for orchestrated cooperative cancer treatment. The nanoreactors are constructed from responsive polyprodrug polymersomes incorporating ultrasmall iron oxide nanoparticles and glucose oxidase in the membranes and inner aqueous cavities, respectively. The cascade reactions including glucose consumption to generate HO, accelerated iron ion release, Fenton reaction between HO and iron ion to produce hydroxyl radicals (•OH), and •OH-triggered rapid release of parent drugs can be specifically activated by the tumor acidity-responsive membrane permeability. During this process, the orchestrated cooperative cancer therapy including starving therapy, chemodynamic therapy, and chemotherapy is realized for high-efficiency tumor suppression by the in situ consumed and produced compounds. The nanoreactor design with tumor-activable cascade reactions represents an insightful paradigm for precise cooperative cancer therapy.
治疗性纳米反应器在精确癌症治疗中越来越受到关注，它们已被探索用于在靶部位原位将惰性前药或内在分子转化为治疗性化合物。然而，工程化具有肿瘤激活级联反应的纳米反应器以实现高效协同癌症治疗仍然是一个巨大的挑战。在此，我们展示了一种聚合物囊泡纳米反应器，其具有肿瘤酸性响应的膜通透性，以激活级联反应，从而进行协调的协同癌症治疗。纳米反应器由响应性多前药聚合物囊泡构建而成，其中在膜中和内水腔中分别包含超小氧化铁纳米粒子和葡萄糖氧化酶。级联反应包括葡萄糖消耗以产生 HO、加速铁离子释放、HO 和铁离子之间的芬顿反应以产生羟基自由基 (•OH) 以及•OH 触发母体药物的快速释放，可以被肿瘤酸性响应的膜通透性特异性激活。在此过程中，通过原位消耗和产生的化合物，实现了饥饿治疗、化学动力学治疗和化学治疗的协同癌症治疗，从而高效抑制肿瘤。具有肿瘤激活级联反应的纳米反应器设计为精确协同癌症治疗提供了一个有见地的范例。
