Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072, Tianjin, PR China.
School of Precision Instruments and Optoelectronics Engineering, Tianjin University, Tianjin 300072, China.
Biomater Sci. 2020 Mar 31;8(7):1981-1995. doi: 10.1039/c9bm02014d.
Improving the generation of reactive oxygen species (ROS) while consuming glutathione (GSH) is the main method for amplifying intracellular oxidative stress. However, in previous studies, it was normally necessary to combine two or more materials to achieve the effect of destroying the intracellular redox homeostasis. This made the preparation process relatively complicated. Herein, we designed ultra-small bismuth sulfide quantum dot (Bi2S3 QD)-doped hollow mesoporous Prussian blue (HMPB) (HMPB/Bi2S3) nanocubes for amplified tumor oxidative stress to augment photo-/radiotherapy. In addition to being photothermal materials, Prussian blue can be used as both a catalyst for the Fenton reaction and a consumer of GSH due to the multivalent state of iron. Ferrous ions (Fe(ii)) can produce toxic ROS-hydroxyl radicals (˙OH) with abundant hydrogen peroxide in the tumor cells by the Fenton reaction. Meanwhile, ferric ions (Fe(iii)) can oxidize the intracellular GSH to GSSG, thus depleting the concentration of GSH inside tumors. As a result, oxidative stress imbalance could be induced by the reversible redox property of Fe(ii/iii), thereby causing DNA damage and increasing the cell membrane permeability to realize enhanced photo-/radiotherapy. As a sensitizer for radiotherapy, ultra-small Bi2S3 QDs (3-5 nm) are doped in HMPB, thus improving the therapeutic effect by prolonging blood circulation and reducing systemic toxicity via kidney metabolism. Therefore, such a reversible HMPB/Bi2S3 nanocube is a promising therapeutic agent for amplified tumor oxidative stress to augment photo-/radiotherapy, which might show further applications in nanomedical science.
增强活性氧 (ROS) 的生成同时消耗谷胱甘肽 (GSH) 是放大细胞内氧化应激的主要方法。然而,在以前的研究中,通常需要结合两种或更多材料来达到破坏细胞内氧化还原平衡的效果。这使得制备过程相对复杂。在此,我们设计了超小的硫化铋量子点 (Bi2S3 QD) 掺杂的中空介孔普鲁士蓝 (HMPB) (HMPB/Bi2S3) 纳米立方来放大肿瘤氧化应激以增强光/放疗。除了作为光热材料外,普鲁士蓝还可以用作 Fenton 反应的催化剂和 GSH 的消耗剂,因为铁具有多价态。亚铁离子 (Fe(ii)) 可以通过 Fenton 反应在肿瘤细胞中产生大量过氧化氢的毒性 ROS-羟基自由基 (˙OH)。同时,三价铁离子 (Fe(iii)) 可以将细胞内的 GSH 氧化为 GSSG,从而耗尽肿瘤内 GSH 的浓度。因此,Fe(ii/iii) 的可逆氧化还原特性可以诱导氧化应激失衡,从而导致 DNA 损伤并增加细胞膜通透性,以实现增强的光/放疗。作为放疗的敏化剂,超小的 Bi2S3 QD(3-5nm)掺杂在 HMPB 中,通过延长血液循环和通过肾脏代谢减少全身毒性来提高治疗效果。因此,这种可逆的 HMPB/Bi2S3 纳米立方是一种有前途的治疗剂,可用于放大肿瘤氧化应激以增强光/放疗,这可能在纳米医学科学中显示出进一步的应用。