School of Life Sciences, Tianjin University, Tianjin, 300072, P. R. China.
Shandong Medical Imaging Research Institute, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, P. R. China.
Adv Mater. 2021 May;33(21):e2100398. doi: 10.1002/adma.202100398. Epub 2021 Apr 19.
An ideal nanotheranostic agent should be able to achieve efficient tumor accumulation, retention, and fast elimination after its theranostic functions exhausts. However, there is an irreconcilable contradiction on optimum sizes for effective tumor retention and fast elimination. Herein, a programmed size-changeable nanotheranostic agent based on polyprodrug-modified iron oxide nanoparticles (IONPs) and aggregation-induced emission photosensitizer is developed for enhanced magnetic resonance imaging (MRI)-guided chemo/photodynamic combination therapy. The nano-sized theranostic agents with an initial diameter of about 90 nm can accumulate in tumor tissue through passive targeting. In the acidic tumor microenvironment, large aggregates of IONPs are formed, realizing enhanced tumor retention and MR signal enhancement. Under the guidance of MRI, light irradiation is applied to the tumor site for triggering the generation of reactive oxygen species and drug release. Moreover, after chemo/photodynamic combination therapy, the large-sized aggregates are re-dispersed into small-sized IONPs for fast elimination, reducing the risk of toxicity caused by long-term retention. Therefore, this study provides a promising size-changeable strategy for the development of nanotheranostic agents.
理想的纳米诊疗剂应该能够在其治疗功能耗尽后实现高效的肿瘤积累、保留和快速消除。然而，在有效肿瘤保留和快速消除的最佳尺寸上存在不可调和的矛盾。本文开发了一种基于多前药修饰的氧化铁纳米粒子（IONPs）和聚集诱导发射光敏剂的可编程尺寸变化的纳米诊疗剂，用于增强磁共振成像（MRI）引导的化疗/光动力联合治疗。初始直径约为 90nm 的纳米级诊疗剂可以通过被动靶向在肿瘤组织中积累。在酸性肿瘤微环境中，形成了 IONPs 的大聚集体，实现了增强的肿瘤保留和磁共振信号增强。在 MRI 的引导下，对肿瘤部位进行光照以触发活性氧的产生和药物释放。此外，在化疗/光动力联合治疗后，大尺寸的聚集体重新分散成小尺寸的 IONPs 以快速消除，降低了长期保留引起毒性的风险。因此，本研究为纳米诊疗剂的发展提供了一种有前途的尺寸变化策略。
