CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Adv Mater. 2019 Apr;31(15):e1808200. doi: 10.1002/adma.201808200. Epub 2019 Feb 18.
Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle-based PDT agent, combining a tumor-targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr-metal-organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism-based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.
光动力疗法（PDT）是一种有前途的抗癌治疗方法，已在临床上批准用于治疗不同类型的肿瘤。然而，目前的 PDT 存在几个障碍，包括其在肿瘤组织中被过量谷胱甘肽（GSH）中和，以及强烈的促血管生成肿瘤反应。在这项工作中，开发了一种仿生多功能纳米颗粒 PDT 制剂，将肿瘤靶向光敏剂与 GSH 清除和抗血管生成治疗相结合。一个卟啉 Zr 金属有机骨架纳米颗粒同时用作光敏剂和血管内皮生长因子受体 2（VEGFR2）抑制剂阿帕替尼的递送载体。核心纳米颗粒被 MnO 包裹以消耗肿瘤内的 GSH，然后用肿瘤细胞膜伪装进行修饰。静脉注射后，纳米颗粒通过同种型靶向介导的仿生修饰选择性地在肿瘤中积累，增强 PDT 和抗血管生成药物的联合使用显著提高了它们的肿瘤抑制效率。这项研究为基于机制的 PDT 增强提供了一个综合解决方案，并展示了多功能纳米系统在肿瘤治疗中的应用的令人鼓舞的潜力。
