Although upconversion photodynamic therapy (PDT) has gained extensive interests in disease treatment, the intracellular migration pathway of upconversion photosensitizers and underlying cell-particle interaction mechanism is still largely unexplored. In this work photoswitchable upconversion nanoparticles (UCNPs) are reported that can release orthogonal emissions excited by two near-infrared lights, i.e., red color of 980-nm and green color of 808-nm light excitation. Taking advantage of the dual-emissive property, a methodology based on Pearson’s correlation analysis is proposed to verify the accuracy of upconversion luminescence signals under different excitation lights, which has been previously neglected. Meanwhile, we have designed a near-infrared mediated bioimaging nanoplatform that can generate reactive oxygen species (ROS) using one light and simultaneously track the location of upconversion photosensitizers using another excitation light. Our study not only depicts the migration pathway of upconversion photosensitizers, but also demonstrates the organelle escape of these upconversion nanoparticles via PCI (photochemical internalization) process. It is believed that our results inspire more efficient synergistic therapy by combining PDT with other modalities in a programmable manner.

Graphical abstract

中文翻译：

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近红外介导的正交生物成像和上转换纳米光敏剂的细胞内跟踪

尽管上转换光动力疗法（PDT）在疾病治疗中获得了广泛的关注，但上转换光敏剂的细胞内迁移途径和潜在的细胞-粒子相互作用机制仍然很大程度上未探索。在这项工作中，光可切换上转换纳米粒子 (UCNPs) 被报道可以释放由两种近红外光激发的正交发射，即 980 纳米的红色和 808 纳米光激发的绿色。利用双发射特性，提出了一种基于 Pearson 相关分析的方法来验证在不同激发光下上转换发光信号的准确性，这是以前被忽略的。同时，我们设计了一种近红外介导的生物成像纳米平台，它可以使用一种光产生活性氧 (ROS)，同时使用另一种激发光跟踪上转换光敏剂的位置。我们的研究不仅描绘了上转换光敏剂的迁移途径，还展示了这些上转换纳米粒子通过 PCI（光化学内化）过程逃逸的细胞器。相信我们的结果通过以可编程方式将 PDT 与其他方式相结合，激发了更有效的协同治疗。但也证明了这些上转换纳米粒子通过 PCI（光化学内化）过程逸出细胞器。相信我们的结果通过以可编程方式将 PDT 与其他方式相结合，激发了更有效的协同治疗。但也证明了这些上转换纳米粒子通过 PCI（光化学内化）过程逸出细胞器。相信我们的结果通过以可编程方式将 PDT 与其他方式相结合，激发了更有效的协同治疗。

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