Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy
Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy
复制标题
肿瘤触发的嵌合肽几何形状转换，用于增强体内肿瘤内化和光动力治疗
DOI：
10.1021/acsnano.7b00216
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发表时间：
2017-03-01
期刊：
影响因子：
17.1
通讯作者：
Han, Heyou
中科院分区：
文献类型：
--
作者：
Han, Kai;Zhang, Jin;Han, Heyou
纳米颗粒的几何形状在细胞内化过程中起着重要作用。然而，其在肿瘤选择性治疗中的适用性仍鲜有报道。在本文中，我们设计了一种具有几何形状开关的肿瘤细胞外酸反应嵌合肽，用于增强肿瘤内化和光动力治疗。该嵌合肽在生理条件下可自组装成球形纳米颗粒。在肿瘤细胞外酸性微环境下，嵌合肽发生了酸敏感的2,3-二甲基马来酸酐基团的分离。随后嵌合肽之间离子互补性的恢复导致棒状纳米颗粒的形成。体外和体内研究均表明，这种酸度触发的几何形状开关赋予嵌合肽加速在肿瘤细胞内的内化，延长在肿瘤组织中的积累，增强光动力治疗，并且副作用最小。我们的研究结果表明，融合微环境与几何形状开关应该是一种有前途的靶向给药策略。
Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rodlike nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.