State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.
Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China.
ACS Appl Mater Interfaces. 2020 Apr 29;12(17):19313-19323. doi: 10.1021/acsami.0c03432. Epub 2020 Apr 20.
Though emerging as a promising therapeutic approach for cancers, the crucial challenge for photodynamic therapy (PDT) is activatable phototoxicity for selective cancer cell destruction with low "off-target" damage and simultaneous therapeutic effect prediction. Here, we design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with self-corrected therapeutic effect prediction. The upconversion nanoprobe is composed of multishelled upconversion nanoparticles (UCNPs) NaYF:Gd@NaYF:Er,Yb@NaYF:Nd,Yb, which covalently modified with an antenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation, photosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect prediction, and CaB substrate peptide labeled with a QSY7 quencher. The energy of UCNPs emission at 540 nm is transferred to Cy3/RB and eventually quenched by QSY7 via two continuous luminance resonance energy transfer processes from interior UCNPs to its surface-extended QSY7. The intracellular CaB specifically cleaves peptide to release QSY7, which correspondingly activates RB with reactive oxygen species (ROS) generation for PDT and recovers Cy3 luminance for CaB imaging. UCNPs emission at 540 nm remains unchanged during the peptide cleavage process, which is served as an internal standard for Cy3 luminance correction, and the fluorescence intensity ratio of Cy3 over UCNPs (FI583/FI540) is measured for self-corrected therapeutic effect prediction. The proposed self-corrected upconversion nanoprobe implies significant potential in precise tumor therapy.
尽管光动力疗法（PDT）作为一种有前途的癌症治疗方法已经出现，但对于选择性杀伤癌细胞的 PDT，其关键挑战是需要具有可激活的光毒性，同时实现低“脱靶”损伤和协同治疗效果预测。在这里，我们设计了一种用于细胞内组织蛋白酶 B（CaB）响应 PDT 的上转换纳米探针，具有自我校正的治疗效果预测功能。该上转换纳米探针由多壳层上转换纳米粒子（UCNPs）NaYF:Gd@NaYF:Er,Yb@NaYF:Nd,Yb 组成，通过共价键修饰了一个天线分子 800CW，用于在近红外辐射下增强 UCNPs 的亮度，光敏剂 Rose Bengal（RB）用于 PDT，Cy3 用于治疗效果预测，以及用 QSY7 淬灭剂标记的 CaB 底物肽。540nm 处的 UCNPs 发射能量通过两个连续的亮度共振能量转移过程从内部 UCNPs 转移到其表面扩展的 QSY7，被 Cy3/RB 最终猝灭。细胞内 CaB 特异性切割肽以释放 QSY7，这相应地激活 RB 产生活性氧（ROS）用于 PDT，并恢复 Cy3 亮度用于 CaB 成像。在肽切割过程中，540nm 处的 UCNPs 发射保持不变，作为 Cy3 亮度校正的内部标准，测量 Cy3 相对于 UCNPs 的荧光强度比（FI583/FI540），用于自我校正的治疗效果预测。所提出的自我校正上转换纳米探针在精确肿瘤治疗中具有重要的潜在应用价值。
