Engineering Research Center of Molecular-imaging and Neuro-imaging of Ministry of Education, School of Life Science and Technology, Xidian University , Xi'an, Shaanxi 710126, China.
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892, United States.
ACS Nano. 2018 Jan 23;12(1):455-463. doi: 10.1021/acsnano.7b06852. Epub 2018 Jan 5.
This study applies in situ production of hypochlorous acid (HOCl) to improve the therapeutic efficacy of platinum drugs. The phagocytic enzyme myeloperoxidase (MPO) is coated with two functional polyphenol derivatives (platinum prodrug polyphenols and PEG polyphenols) and ferric ion by metal phenolic coordination, which can shield MPO from degradation by other compounds in the blood. Moreover, the platinum prodrug can be reduced to cisplatin in cells and produce hydrogen peroxide (HO). The MPO catalyzes the conversion of HO to HOCl in the intercellular environment. The as-prepared MPO Pt PEG nanoparticles (MPP NPs) can be employed as a reactive oxygen species cascade bioreaction to enhance platinum drug therapy. The MPP NPs show prolonged blood circulation and high tumor accumulation as evidenced by Zr-based positron emission tomography imaging. The MPP NPs effectively inhibit tumor growth in vivo. As a first-in-class platform to harness the highly toxic HOCl in nanomedicine for cancer therapy, this strategy may open doors for further development of progressive therapeutic systems.
本研究应用原位生成次氯酸（HOCl）来提高铂类药物的治疗效果。吞噬酶髓过氧化物酶（MPO）通过金属酚配位被两种功能性多酚衍生物（铂前药多酚和 PEG 多酚）和铁离子包裹，这可以防止 MPO 被血液中的其他化合物降解。此外，铂前药可以在细胞内还原为顺铂并产生过氧化氢（HO）。MPO 在细胞外环境中催化 HO 转化为 HOCl。所制备的 MPO-Pt-PEG 纳米颗粒（MPP NPs）可用作活性氧级联生物反应以增强铂类药物治疗效果。Zr 基正电子发射断层扫描成像表明，MPP NPs 具有延长的血液循环时间和高肿瘤积累。MPP NPs 有效地抑制了体内肿瘤的生长。作为一类利用纳米医学中高毒性 HOCl 治疗癌症的首创平台，该策略可能为进一步开发渐进式治疗系统开辟道路。
