State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China.
UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Biomaterials. 2021 Jun;273:120807. doi: 10.1016/j.biomaterials.2021.120807. Epub 2021 Apr 7.
Previous preclinical and clinical studies have shown that using only a single therapy makes it difficult to completely eradicate tumors and restrain cancer metastasis. To overcome this challenge, multi-modal synergistic treatments have attracted considerable attention. Herein, an ultrathin Cu-loaded CoCuFe-selenide (CCFS) was prepared by a facile topotactic transformation from CoCuFe layered double hydroxide (LDH) nanosheets (NSs), followed by surface modification with polyvinyl pyrrolidone (PVP) and l-arginine (L-Arg). The resultant CCFS-PVP-L-Arg (CPA) system shows excellent synergetic photothermal and gas therapy (PTT/GT). The CCFS NSs have strong LSPR absorbance characteristic, with enhanced light absorption in the near-infrared (NIR) region. This endows the CPA nanocomposite with an outstanding photothermal conversion efficiency of 72.0% (pH 7.4) and 81.0% (pH 5.4), among the highest reported for 2D chalcogenide nanomaterials. In addition, NO release from CPA is triggered by decomposition of L-Arg in the HO-rich and acidic tumor microenvironment, permitting localized NO gas therapy in the tumor site. In vitro experiments revealed 91.8% apoptosis of HepG2 cells, and in vivo studies showed complete tumor elimination upon treatment with the CPA nanocomposite under NIR irradiation. To the best of our knowledge, this is the first report of combined defect-induced high-efficiency PTT with HO and pH targeted GT.
先前的临床前和临床研究表明，仅使用单一疗法很难完全根除肿瘤并抑制癌症转移。为了克服这一挑战，多模式协同治疗引起了广泛关注。在此，通过从 CoCuFe 层状双氢氧化物（LDH）纳米片（NS）进行简便的拓扑转化，制备了超薄的负载铜的 CoCuFe 硒化物（CCFS），然后用聚乙烯吡咯烷酮（PVP）和 l-精氨酸（L-Arg）进行表面修饰。所得的 CCFS-PVP-L-Arg（CPA）体系表现出优异的光热和气体协同治疗（PTT/GT）。CCFS NS 具有强的 LSPR 吸收特性，在近红外（NIR）区域增强了光吸收。这使 CPA 纳米复合材料具有出色的光热转换效率，在 pH 值为 7.4 时为 72.0%，在 pH 值为 5.4 时为 81.0%，是报道的二维硫属化物纳米材料中最高的之一。此外，CPA 中的 NO 释放是由 HO 丰富和酸性肿瘤微环境中 L-Arg 的分解触发的，允许在肿瘤部位进行局部 NO 气体治疗。体外实验显示 HepG2 细胞的凋亡率达到 91.8%，体内研究表明，在近红外照射下用 CPA 纳米复合材料治疗后完全消除了肿瘤。据我们所知，这是首次报道将缺陷诱导的高效 PTT 与 HO 和 pH 靶向 GT 相结合。
