State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
Department of Chemistry, Brown University, Providence, RI, 02912, USA.
Biomaterials. 2021 Jan;268:120530. doi: 10.1016/j.biomaterials.2020.120530. Epub 2020 Nov 28.
The iron-based Fenton-type reaction has drawn tremendous attention in cancer therapy. Compared with oxidized iron, Fe(0) possesses high catalytic activity but unstable for biomedical application. Here, we report a new strategy to stabilize Fe(0) via a porous yolk shell nanostructure of Fe/FeO (PYSNPs) in normal physiological condition, and to control the release of Fe(0) in tumor microenvironment for enhanced cancer therapy. These PYSNPs display superior tumor inhibition with the IC down to 20 μg/mL (over 1 mg/mL for iron oxide nanoparticles as control) for HepG2 cell. A single intravenous injection of as low as 1 mg/kg dosage is effective to suppress tumor growth in vivo. Moreover, the disintegration of PYSNPs in the acidic tumor microenvironment could cause significant change in MRI signal for contrast-enhanced diagnosis. Of note, the resulting FeO fragments are renal clearable with minimized side effect. In all, this work represented a nanoplatform to stabilize and selectively deliver Fe(0) for highly effective cancer therapy.
基于铁的芬顿型反应在癌症治疗中引起了极大的关注。与氧化铁相比，Fe(0)具有高催化活性，但在生物医学应用中不稳定。在这里，我们报告了一种通过多孔蛋黄壳纳米结构的 Fe/FeO（PYSNPs）在正常生理条件下稳定 Fe(0)的新策略，并控制其在肿瘤微环境中的释放，以增强癌症治疗效果。这些 PYSNPs 对 HepG2 细胞的抑制作用显著，IC 低至 20μg/mL（对照组氧化铁纳米颗粒为 1mg/mL 以上）。仅需低至 1mg/kg 的单次静脉注射剂量即可有效抑制体内肿瘤生长。此外，PYSNPs 在酸性肿瘤微环境中的崩解会导致 MRI 信号发生显著变化，从而进行对比增强诊断。值得注意的是，生成的 FeO 碎片可被肾脏清除，副作用最小。总之，这项工作代表了一种纳米平台，可用于稳定和选择性递送 Fe(0)，以实现高效的癌症治疗。
