Tumor-triggered transformation of chimeric peptide for dual-stage-amplified magnetic resonance imaging and precise photodynamic therapy
Tumor-triggered transformation of chimeric peptide for dual-stage-amplified magnetic resonance imaging and precise photodynamic therapy
复制标题
用于双级放大磁共振成像和精确光动力治疗的嵌合肽的肿瘤触发转化
DOI：
10.1016/j.biomaterials.2018.08.026
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发表时间：
2018
期刊：
影响因子：
14
通讯作者：
Han He You
中科院分区：
文献类型：
--
作者：
Zhang Jin;Mu Yong Li;Ma Zhao Yu;Han Kai;Han He You
尽管在临床磁共振成像（MRI）中取得了巨大的成功，但基于Gd 3+的造影剂仍然遭受低质子弛豫效率、快速代谢清除以及低灵敏度。在这项工作中，我们设计了一个基质金属蛋白酶-2（MMP-2）响应嵌合肽的双阶段放大MRI和精确的光动力学治疗。体外和体内研究表明，该嵌合肽在生理条件下可以自组装成球形纳米颗粒，r1值为28.17 mM− 1 s −1。同时，球形嵌合肽通过增强的穿透和滞留（EPR）效应，赋予其有效的肿瘤蓄积。更重要的是，肿瘤区域过表达的MMP-2可以特异性地水解嵌合肽，导致球向纤维的转化。这种转化增强了肿瘤的积聚和造影剂的弛豫。因此，r1值显著升高至51.52 mM− 1 s −1，这指导了精确的光动力治疗。这种肿瘤微环境触发的可转化策略将显示出肿瘤靶向成像和光疗的巨大潜力。
Despite the great success in clinical magnetic resonance imaging (MRI), Gd3+-based contrast agents still suffer from low proton relaxation efficiency, rapid metabolic clearance as well as poor sensitivity. In this work, we designed a matrix metalloproteinase-2 (MMP-2) responsive chimeric peptide for dual-stage-amplified MRI and precise photodynamic therapy. Bothin vitroandin vivostudies indicated that this chimeric peptide could self-assembly into spherical nanoparticles at physiological condition with r1value of 28.17 mM−1s−1. Meanwhile, the spherical shape endowed chimeric peptide with efficient tumor accumulationviaenhanced penetration and retention (EPR) effect. Importantly, the overexpressed MMP-2 in tumor region could specifically hydrolyze chimeric peptide, leading to sphere-to-fiber transformation. This transformation enhanced both the tumor accumulation and the relaxivity of contrast agent. Consequently, the r1value was remarkably elevated to 51.52 mM−1s−1, which guided precise photodynamic therapy. This tumor microenvironment-triggered transformable strategy should show great potential for tumor-targeted imaging and phototherapy.