Department of Pharmacy, Hangzhou Third People's Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
J Nanobiotechnology. 2023 Sep 19;21(1):335. doi: 10.1186/s12951-023-02090-z.
Calcium (Ca) 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 Ca 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 Ca. The synergistic Ca overload mediated by photonanomedicine exhibited an enhanced and superior anti-tumor efficacy. We believe this photonanomedicine expands the toolbox to manipulate intracellular Ca concentration and holds a great potential as an anti-tumor therapy.
钙（Ca）对于线粒体的稳态和功能协调至关重要，特别是在经常代谢以维持其生长的癌细胞中。光化学介导的钙超载已成为抑制肿瘤的有效方法，引起了广泛关注。在此，我们开发了一种光纳米药物，通过细胞表面光化学协同诱导钙超载，从而实现肿瘤抑制。具体来说，将光敏剂原卟啉 IX（PpIX）负载到上转换纳米粒子（UCNP）上，随后用带有光交联肉桂酸（CA）基团的聚合物对其进行修饰。所得纳米粒子进一步通过抗 CD20 适体（Apt）进行功能化，得到光纳米药物。CD20 受体与抗 CD20 适体之间的相互作用使光纳米药物在静脉注射后能够准确地附着在 Raji 细胞表面。局部应用 980nm 近红外激光后，光纳米药物能够捕获近红外光并将其转化为紫外线（UV）光。一方面，转化的 UV 光导致光纳米药物中肉桂酸基团的交联，进一步刺激 CD20 受体的聚集，导致 Ca 内流。另一方面，UV 光可以同时激发 PpIX 原位产生活性氧（ROS），破坏细胞膜的完整性，导致 Ca 内流。光纳米药物介导的协同钙超载表现出增强和优越的抗肿瘤功效。我们相信，这种光纳米药物扩展了操纵细胞内 Ca 浓度的工具包，并具有作为抗肿瘤治疗的巨大潜力。
