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In vivo self-degradable graphene nanomedicine operated by DNAzyme and photo-switch for controlled anticancer therapy
Biomaterials ( IF 14.0 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.biomaterials.2020.120402
Hyori Lee , Jinhwan Kim , Junseok Lee , Hyeongmok Park , Yohwan Park , Sungjin Jung , Junha Lim , Hee Cheul Choi , Won Jong Kim

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.



中文翻译:

DNAzyme和光敏开关在体内可降解石墨烯纳米药物的控制抗癌治疗

尽管氧化石墨烯(GO)本身具有许多有益于生物医学用途的功能,但对于体内应用而言,不可避免地要用几种聚合物或蛋白质修饰GO表面。然而,由于空间位阻,这种修饰限制了GO的降解性。在这种情况下,非常需要设计一种表面修饰的GO载体,该载体将在其生物学功能(即药物递送)后降解,尤其是在复杂的体内水平。在本文中,我们通过应用催化性DNA设计了前所未有的“催化性GO纳米药物”,经过表面修饰后的治疗后,GO在体内全身水平实现了GO的自降解。一旦粘蛋白1(MUC1)适体促进内吞作用吸收了催化性GO纳米药物,光开关就会触发阿霉素从DNA的释放。GO表面上的单链G-四链体序列形成四重结构并通过与GO表面上的血红素结合而成为DNA核酶,表现出过氧化物酶作用。由于癌细胞中过高的H2O2浓度,催化型GO纳米药物会生成足够量的强氧化剂次氯酸(HOCl),从而将GO降解成小碎片,从而可能清除。体内环境。

更新日期:2020-09-20
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