Wu Hongshuai, Gu Dihai, Xia Shengjin, Chen Fanghui, You Chaoqun, Sun Baiwang
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
Biomater Sci. 2021 Feb 7;9(3):1020-1033. doi: 10.1039/d0bm01734e. Epub 2020 Dec 16.
Reasonable management of the one-for-all nanoplatform can facilitate improved cancer therapy. Here, the metal-organic frameworks (MOFs) based on iron(iii) carboxylate material (MIL-101-NH) were in situ decorated on stabilized polydopamine nanoparticles (PDANPs), which subsequently loaded glucose oxidase (GOx) via hyaluronic acid (HA) coating to structure the one-for-all intelligent core-shell nanoparticles (HG-MIL@PDANPs). Because of the inner PDANPs, the HG-MIL@PDANPs could realize near-infrared (NIR)-controllable site-specific photothermal therapy (PTT). Additionally, the core-shell nanoparticles exhibited a pH-triggered and NIR-reinforced release of Fe and GOx owing to the controllable degradation of the outer shell. Hydroxyl radicals (˙OH) were produced for chemodynamic therapy (CDT) employing the Fe-driven Fenton reaction, which could be greatly promoted by Fe-involved glutathione (GSH) depletion and GOx-catalyzed acidity recovery and HO self-sufficiency. Moreover, the HA ligand could enhance the tumor accumulation of the HG-MIL@PDANPs through the long blood circulation time and CD44-targeted cell recognition. The ingenious integration of PTT and CDT in one fully equipped system presented excellent synergistic antitumor efficiency in vitro and in vivo with favorable biosafety. The one-for-all intelligent core-shell nanoparticles with CD44 targeting provide a new avenue for engineering on-demand tumor-specific therapy.
对通用纳米平台进行合理管理有助于改善癌症治疗。在此，基于羧酸铁（III）材料（MIL-101-NH）的金属有机框架（MOF）原位修饰在稳定的聚多巴胺纳米颗粒（PDANP）上，随后通过透明质酸（HA）包被负载葡萄糖氧化酶（GOx），构建了通用智能核壳纳米颗粒（HG-MIL@PDANP）。由于内部的PDANP，HG-MIL@PDANP能够实现近红外（NIR）可控的位点特异性光热疗法（PTT）。此外，由于外壳的可控降解，核壳纳米颗粒表现出pH触发和NIR增强的铁和GOx释放。利用铁驱动的芬顿反应产生羟基自由基（˙OH）用于化学动力学疗法（CDT），铁参与的谷胱甘肽（GSH）消耗、GOx催化的酸度恢复和HO自给自足可极大促进该反应。此外，HA配体可通过延长血液循环时间和CD44靶向细胞识别增强HG-MIL@PDANP在肿瘤中的积累。PTT和CDT在一个全功能系统中的巧妙整合在体外和体内均呈现出优异的协同抗肿瘤效果，且具有良好的生物安全性。具有CD44靶向性的通用智能核壳纳米颗粒为按需进行肿瘤特异性治疗工程提供了一条新途径。
