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双催化级联纳米平台用于光/化学动力学/饥饿协同治疗。

Dual catalytic cascaded nanoplatform for photo/chemodynamic/starvation synergistic therapy.

机构信息

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, PR China.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, PR China.

出版信息

Colloids Surf B Biointerfaces. 2021 Mar;199:111538. doi: 10.1016/j.colsurfb.2020.111538. Epub 2020 Dec 21.

Abstract

In this study, manganese dioxide (MnO) was attached to prussian blue (PB) by a one-pot method to prepare PBMO. Then, the GOD was loaded onto PBMO through the electrostatic interaction of hyaluronic acid (HA) to form tumor-targeted nanoplatform (PBMO-GH). Hydrogen peroxide (HO) and gluconic acid were produced through the GOD-catalyzed enzymatic reaction. Meanwhile, PB could not only catalyze HO for oxygen generation to further promote glucose consumption but also possess the property of photothermal conversion. As a result, glucose was continuously consumed to achieve the starvation therapy (ST), and the photothermal therapy (PTT) could be realized under near-infrared (NIR) light. Besides, the Mn generated by the reaction of MnO with glutathione (GSH) could exert Fenton-like reaction to produce highly toxic hydroxyl radicals (·OH) from HO, which thereby realized self-reinforcing chemodynamic therapy (CDT). In vitro and in vivo experiments demonstrated that PBMO-GH could effectively inhibit the growth of tumor cells via ST/CDT/PTT synergistic effect. Therefore, the as-prepared nanoplatform for multi-modal therapy will provide a promising paradigm for overcoming cancer.

摘要

在这项研究中,通过一锅法将二氧化锰(MnO)附着到普鲁士蓝(PB)上,制备 PBMO。然后,通过透明质酸(HA)的静电相互作用将 GOD 加载到 PBMO 上,形成肿瘤靶向纳米平台(PBMO-GH)。通过 GOD 催化的酶反应产生过氧化氢(HO)和葡萄糖酸。同时,PB 不仅可以催化 HO 产生氧气以进一步促进葡萄糖消耗,而且还具有光热转换的特性。因此,葡萄糖被持续消耗以实现饥饿治疗(ST),并且可以在近红外(NIR)光下实现光热治疗(PTT)。此外,MnO 与谷胱甘肽(GSH)反应生成的 Mn 可以发挥类芬顿反应,从 HO 中产生高毒性的羟基自由基(·OH),从而实现自增强的化学动力学治疗(CDT)。体外和体内实验表明,PBMO-GH 可以通过 ST/CDT/PTT 协同作用有效抑制肿瘤细胞的生长。因此,这种多模式治疗的纳米平台为克服癌症提供了一种很有前途的范例。

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