钙（Ca2+）对线粒体的稳态和功能协调至关重要，尤其对需要频繁代谢以维持生长的癌细胞而言。光化学介导的钙超载作为一种有效的抑制肿瘤的途径受到了广泛关注。在本研究中，我们开发了一种光纳米医药物，通过细胞表面光化学反应协同诱导钙超载以达到抑制肿瘤的效果。具体而言，光敏剂原卟啉IX（PpIX）被载入上转换纳米颗粒（UCNP），并进一步修饰成携带光交联肉桂酸酯（CA）基团的聚合物。最终的纳米颗粒被抗CD20适配体（Apt）功能化，形成光纳米医药物。CD20受体与抗CD20适配体之间的相互作用使光纳米医药物能够在静脉注射后准确地附着在Raji细胞表面。在局部应用980 nm近红外激光后，光纳米医药物能够捕获近红外光并将其转化为紫外光。一方面，转化后的紫外光引发了光纳米医药物中肉桂酸酯基团的交联，进一步刺激CD20受体的聚集并导致钙离子内流。另一方面，紫外光可同时激发PpIX产生原位活性氧（ROS），破坏细胞膜完整性并导致钙离子内流。光纳米医药物介导的协同钙超载表现出增强和优越的抗肿瘤疗效。我们相信，这种光纳米医药物扩展了操控细胞内钙离子浓度的工具箱，并具有作为抗肿瘤疗法的巨大潜力。© 2023. BioMed Central Ltd., part of Springer Nature.

Calcium (Ca2+) is essential for mitochondrial homeostasis and function coordination, particularly in cancer cells that metabolize frequently to sustain their growth. Photochemistry mediated calcium overload has attracted lots of attention as an effective way to achieve tumor suppression. Herein, we developed a photonanomedicine to synergistically induce calcium overload via cell-surface photochemistry and thus tumor suppression. Specifically, the photosensitizer, protoporphyrin IX (PpIX) was loaded onto upconversion nanoparticles (UCNP), which was subsequently modified by a polymer bearing photo-crosslinking cinnamate (CA) groups. The resulting nanoparticle was further functionalized by anti-CD20 aptamers (Apt), to give photonanomedicine. The interaction between CD20 receptors and anti-CD20 aptamers allowed photonanomedicine to accurately attach onto the Raji cell surface after an intravenous injection. Following the local application of a 980 nm NIR laser, the photonanomedicine was able to capture the NIR light and convert it into ultraviolet (UV) light. On one hand, the converted UV light led the crosslinking of cinnamate groups in photonanomedicine, further stimulating the clustering of CD20 receptors and causing Ca2+ influx. On the other hand, the UV light could simultaneously excited PpIX to generate reactive oxygen species (ROS) in situ to break down the integrity of cell membrane and lead to an influx of Ca2+. The synergistic Ca2+ overload mediated by photonanomedicine exhibited an enhanced and superior anti-tumor efficacy. We believe this photonanomedicine expands the toolbox to manipulate intracellular Ca2+ concentration and holds a great potential as an anti-tumor therapy.© 2023. BioMed Central Ltd., part of Springer Nature.