In vivo self-degradable graphene nanomedicine operated by DNAzyme and photo-switch for controlled anticancer therapy
In vivo self-degradable graphene nanomedicine operated by DNAzyme and photo-switch for controlled anticancer therapy
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DOI：
10.1016/j.biomaterials.2020.120402
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发表时间：
2020-12-01
期刊：
影响因子：
14
通讯作者：
Kim, Won Jong
中科院分区：
文献类型：
--
作者：
Lee, Hyori;Kim, Jinhwan;Kim, Won Jong
虽然氧化石墨烯本身在生物医学上具有许多有益的功能，但在体内应用中，用几种聚合物或蛋白质修饰氧化石墨烯表面是不可避免的；然而，由于空间位阻的存在，这种改性限制了氧化石墨烯的可降解性。在这种情况下，设计一种表面修饰的氧化石墨烯载体，在其生物功能（即药物递送）后将被降解，这是非常需要的，特别是在复杂的体内水平。在此，我们设计了一种前所未有的“催化氧化石墨烯纳米药物”，通过应用催化DNA，在表面修饰后的治疗后，实现氧化石墨烯在体内系统水平的自降解。一旦催化氧化石墨烯纳米药物被黏液蛋白1 （MUC1）适配体促进的内吞作用所吸收，光开关就会触发DNA释放阿霉素。氧化石墨烯表面的单链g -四重体序列形成四重奏结构，与氧化石墨烯表面的血红蛋白结合成为DNAzyme，表现出过氧化物酶作用。由于癌细胞中高浓度的H2O2，催化氧化石墨烯纳米药物产生足量的强氧化剂次氯酸（HOCl），诱导氧化石墨烯降解成小片段进行潜在清除。我们证明了催化氧化石墨烯纳米药物在细胞和复杂的体内环境中治疗和降解的潜力。
Although graphene oxide (GO) possesses many beneficial functionalities for biomedical usage as itself, modification of GO surface with several polymers or protein is inevitable for in vivo applications; however, such modification limits the degradability of GO due to the steric hindrance. In that context, designing of a surface modified GO carrier that is going to be degraded after its biological function (i.e., drug delivery) is highly desired, especially at complex in vivo level. Herein, we design an unprecedented "catalytic GO nanomedicine" by applying the catalytic DNA, achieving self-degradation of GO in systemic level in the body after the therapy following surface modification. Once the catalytic GO nanomedicines are taken up by mucin1 (MUC1) aptamer-facilitated endocytosis, a photo-switch triggers the release of doxorubicin from the DNA. The single stranded G-quadruplex sequence on the surface of GO forms a quartet structure and becomes DNAzyme by binding with hemin on the GO surface, exhibiting peroxidase effect. Due to the high H2O2 concentration in cancer cells, the catalytic GO nanomedicine generates sufficient amount of strong oxidant, hypochlorous acid (HOCl), inducing GO degradation into small fragments for potential clearance. We demonstrate the potential of our catalytic GO nanomedicine for both therapy and degradation at cellular and complex in vivo environment.