Tumor acidity-activatable manganese phosphate nanoplatform for amplification of photodynamic cancer therapy and magnetic resonance imaging
Tumor acidity-activatable manganese phosphate nanoplatform for amplification of photodynamic cancer therapy and magnetic resonance imaging
复制标题
用于放大光动力癌症治疗和磁共振成像的肿瘤酸度激活磷酸锰纳米平台
DOI：
10.1016/j.actbio.2017.08.028
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发表时间：
2017-10-15
影响因子：
9.7
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
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作者：
Hao, Yongwei;Zheng, Cuixia;Zhang, Yun
无定形可生物降解金属磷酸盐纳米材料被认为在癌症治疗诊断应用中具有巨大的潜力，因为它们有望同时提供超灵敏的pH响应治疗益处和诊断功能。在这里，我们报道了具有超敏感pH响应降解性的光敏和携带吖啶的无定形多孔磷酸锰（PMP）纳米颗粒的合成及其在光活化协同纳米系统中的应用，该系统与缺氧诱导因子1 α/血管内皮生长因子同步赋予活性氧（ROS）诱导的细胞毒性。（HIF 1 α/VEGF）抑制剂，抑制肿瘤生长和治疗逃逸信号通路。羧甲基葡聚糖（CMD）通过pH响应性硼酸酯化学锚定在多孔磷酸锰治疗诊断系统的表面。在肿瘤酸性微环境的刺激下，磷酸锰迅速分解并释放Mn2+离子，这是磁共振成像（MRI）效应的原因。同时，释放的光敏剂二氢卟酚e6（Ce6）在照射下产生ROS，而吖啶黄素（ACF）在光动力疗法（PDT）诱导的肿瘤中VEGF爆发释放期间抑制HIF-1 α/VEGF通路，导致治疗功效增加。考虑到强pH响应性、MRI信号放大和药物释放特性，PMP纳米颗粒通过及时抑制HIF-1 α/VEGF通路来放大PDT，同时增强MRI效应，为肿瘤酸激活治疗诊断应用提供了新的前景。我们报告了肿瘤酸性的合成-可活化的无定形多孔磷酸锰纳米颗粒及其用于赋予活性氧物质（ROS）诱导的细胞毒性与抑制肿瘤生长和治疗逃逸信号通路的缺氧诱导因子1 α/血管内皮生长因子（HIF-1 α/VEGF）抑制剂同步。此外，在肿瘤酸性微环境的刺激下，磷酸锰纳米颗粒最终崩解并迅速释放Mn 2+离子，这是磁共振成像（MRI）效应的原因。这种纳米平台具有独特的优势，如超pH响应药物释放，MRI功能和合理的药物组合，利用治疗逃逸信号通路的阻断。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Amorphous biodegradable metal phosphate nanomaterials are considered to possess great potential in cancer theranostic application due to their promise in providing ultra-sensitive pH-responsive therapeutic benefits and diagnostic functions simultaneously. Here we report the synthesis of photosensitising and acriflavine-carrying amorphous porous manganese phosphate (PMP) nanoparticles with ultra sensitive pH-responsive degradability and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor l alpha/vascular endothelial growth factor (HIF1 alpha/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Carboxymethyl dextran (CMD) is chemically anchored on the surface of porous manganese phosphate theranostic system through the pH-responsive boronate esters. Upon the stimulus of the tumor acid microenvironment, manganese phosphate disintegrates and releases Mn2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. Meanwhile, the released photosensitizer chlorin e6 (Ce6) produces ROS under irradiation while acriflavine (ACF) inhibits the HIF-1 alpha/VEGF pathway during the burst release of VEGF in tumour induced by photodynamic therapy (PDT), resulting in increased therapeutic efficacy. Considering the strong pH responsivity, MRI signal amplification and drug release profile, the PMP nanoparticles offer new prospects for tumor acidity-activatable theranostic application by amplifying the PDT through inhibiting the HIF-1 alpha/VEGF pathway timely while enhancing the MRI effect.Statement of SignificanceIn this study, we report the synthesis of the tumor acidity-activatable amorphous porous manganese phosphate nanoparticles and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor l alpha/vascular endothelial growth factor (HIF-1 alpha/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Besides, upon the stimulus of the tumor acid microenvironment, the manganese phosphate nanoparticles finally disintegrate and release Mn2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. This nanoplatform is featured with distinctive advantages such as ultra pH-responsive drug release, MRI function and rational drug combination exploiting the blockage of the treatment escape signalling pathway. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.