Photodynamic therapy (PDT) has been proposed in cancer treatment for decades, but its clinical translation is significantly impeded by the low yield of ROS, poor tissue penetration depth of most current photosensitizers, and short lifetime of ROS. These limitations directly affect the therapeutic effect of PDT in cancer therapy. Here we proposed a new strategy by collaboratively integrating rare-earth doped upconversion nanoparticles (UCNP) with graphene quantum dot (GQD) for highly efficacious PDT, based on the merits of UCNP, which can emit UV-vis light under near-infrared light (NIR) excitation, and GQD, which can produce ¹O₂ efficiently. For GQD-decorated UCNP nanoparticles (UCNP-GQD), the emission light from UCNP can further excite GQD with prominent ¹O₂ generation for NIR-triggered PDT. Furthermore, a hydrophilic rhodamine derivative, TRITC, is covalently tethered to afford the resultant UCNP-GQD/TRITC, possessing distinct mitochondrial targeting property. Thus mitochondrial specific PDT with in-situ¹O₂ burst in mitochondria induces sharp decrease of mitochondrial membrane potential, which initiates the tumor cell apoptosis irreversibly. Importantly, in vivo experiments demonstrate the tumor inhibition of mitochondrial targeting UCNP-GQD/TRITC with improved therapeutic efficiency compared with non-targeting UCNP-GQD. The proposed strategy highlights the advantages of precision organelles-specific PDT in cancer therapy.

中文翻译：

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稀土纳米粒子介导的近红外石墨烯量子点的线粒体特异性光动力学治疗

在癌症治疗中已经提出了光动力疗法（PDT），但其临床翻译受到ROS产量低，大多数当前光敏剂的组织渗透深度差以及ROS寿命短的阻碍。这些局限性直接影响了PDT在癌症治疗中的治疗效果。在这里，我们基于UCNP的优点，提出了一种将稀土掺杂的上转换纳米粒子（UCNP）与石墨烯量子点（GQD）协同集成以实现高效PDT的新策略，该技术可以在近红外光下发射UV-vis光（ NIR）激发和GQD，可有效产生¹ O ₂。对于装饰有GQD的UCNP纳米颗粒（UCNP-GQD），来自UCNP的发射光可以进一步激发具有显着¹ O的GQD。NIR触发的PDT为₂代。此外，将亲水性罗丹明衍生物TRITC共价束缚，得到具有独特线粒体靶向特性的所得UCNP-GQD / TRITC。因此，线粒体中具有原位¹ O ₂爆发的线粒体特异性PDT诱导线粒体膜电位急剧下降，从而不可逆地启动了肿瘤细胞的凋亡。重要的是，体内实验证明与非靶向UCNP-GQD相比，靶向线粒体靶向UCNP-GQD / TRITC的肿瘤抑制具有更高的治疗效率。提出的策略突出了精确的细胞器专用PDT在癌症治疗中的优势。