School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, P. R. China.
College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, P. R. China.
Small. 2020 Nov;16(45):e2001805. doi: 10.1002/smll.202001805. Epub 2020 Oct 20.
The rational integration of chemotherapy and hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) holds great potential for cancer treatment. Herein, a smart biocompatible nanocatalyst based on porous core-shell cuprous oxide nanocrystals (Cu O-PEG (polyethylene glycol) NCs) is reported for acid-triggered chemo/chemodynamic synergistic therapy. The in situ formed high density of hydrophilic PEG outside greatly improves the stability and compatibility of NCs. The porosity of Cu O-PEG NCs shows the admirable capacity of doxorubicin (DOX) loading (DOX@Cu O-PEG NCs) and delivery. Excitingly, Cu (Cu ) and DOX can be controllably released from DOX@Cu O-PEG NCs in a pH-responsive approach. The released Cu exerts Fenton-like catalytic activity to generate toxic ·OH from intracellular overexpressed hydrogen peroxide (H O ) for CDT via reactive oxygen species (ROS)-involved oxidative damage. Exactly, DOX can not only induce cell death for chemotherapy but also enhance CDT by self-supplying endogenous H O . After the intravenous injection, Cu O-PEG NCs can effectively accumulate in tumor region via passive targeting improved by external high-density PEG shell. Additionally, the effect of boosted CDT combined with chemotherapy presents excellent in vivo antitumor ability without causing distinct systemic toxicity. It is believed that this smart nanocatalyst responding to the acidity provides a novel paradigm for site-specific cancer synergetic therapy.
化疗与羟基自由基（·OH）介导的化学动力学疗法（CDT）的合理整合在癌症治疗方面具有巨大的潜力。在此，报告了一种基于多孔核壳结构氧化亚铜纳米晶体（CuO-PEG（聚乙二醇）NCs）的智能生物相容性纳米催化剂，用于酸触发的化疗/化学动力学协同治疗。原位形成的高密度亲水性 PEG 极大地提高了 NCs 的稳定性和相容性。CuO-PEG NCs 的多孔性表现出令人钦佩的阿霉素（DOX）负载（DOX@CuO-PEG NCs）和递送能力。令人兴奋的是，DOX@CuO-PEG NCs 可以通过 pH 响应方式可控地释放 Cu（Cu2+）和 DOX。释放的 Cu 发挥类芬顿催化活性，从细胞内过表达的过氧化氢（H2O2）生成有毒的·OH，用于 CDT 通过活性氧（ROS）参与的氧化损伤。确切地说，DOX 不仅可以通过化疗诱导细胞死亡，还可以通过自我供应内源性 H2O2 增强 CDT。静脉注射后，CuO-PEG NCs 可以通过外部高密度 PEG 壳增强的被动靶向有效地在肿瘤区域积聚。此外，增强的 CDT 与化疗的联合作用表现出优异的体内抗肿瘤能力，而不会引起明显的全身毒性。相信这种响应酸度的智能纳米催化剂为肿瘤的特异性协同治疗提供了一种新的范例。
