School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, PR China.
School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, PR China.
Colloids Surf B Biointerfaces. 2021 Mar;199:111538. doi: 10.1016/j.colsurfb.2020.111538. Epub 2020 Dec 21.
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.
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。