Getachew Girum, Hsiao Chien-Hua, Wibrianto Aswandi, Rasal Akash S, Batu Dirersa Worku, Huang Chih-Ching, Vijayakameswara Rao Neralla, Chen Je-Hsin, Chang Jia-Yaw
Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, Republic of China.
Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan, Republic of China.
J Colloid Interface Sci. 2023 Mar;633:396-410. doi: 10.1016/j.jcis.2022.11.112. Epub 2022 Nov 26.
The design of therapeutic nanoplatforms based on fluorescent carbon dots (CDs) has become a viable strategy because of their aqueous solubility, biocompatibility, and ease of further functionalization. By doping various heteroatoms into pristine CDs structures, we synthesized N-, Cl-, and S-doped CDs (NClS/CDs), as well as Se-, N-, and Cl-doped CDs (NClSe/CDs) with superior optoelectronic properties using rapid and straightforward microwave heating. The quantum efficiencies of these NClS/CDs and NClSe/CDs were enhanced to 30.7 % and 42.9 %, respectively, compared to those of undoped CDs (0.66 %). Owing to their better light absorption properties, NClS/CDs efficiently produced reactive oxygen species (ROS) under 532 nm laser irradiation for photodynamic therapy (PDT). Considering the ROS generation and surface carrier abilities of NClS/CDs, we designed the loading of camptothecin (CPT) drug via a thioketal linker (TL), resulting in h/CDs@CPT nanovesicles (NVs) with a drug-loading efficiency of 46.5 %. Under laser irradiation in an acidic environment, ROS-triggered CPT release was observed, with 50.2 % of CPT released following the breakdown of the ROS-sensitive TL. In vitro cellular studies revealed that h/CDs@CPT NVs possessed minimal cytotoxicity toward HeLa and 4 T1 cancer cells, despite the high clinical efficacy of PDT and ROS-induced chemotherapeutic response under laser treatment. Confocal microscopy of HeLa and 4 T1 cells revealed that h/CDs@CPT NVs produced red-emissive photographs for potential cancer cell detection. Therefore, our study presents an image-guided PDT and chemotherapeutic platform based on h/CDs@CPT NVs, which will be an attractive candidate for future cancer treatment.
基于荧光碳点（CDs）的治疗性纳米平台设计已成为一种可行策略，这得益于其水溶性、生物相容性以及易于进一步功能化的特点。通过将各种杂原子掺杂到原始CDs结构中，我们使用快速简便的微波加热合成了具有优异光电性能的氮、氯、硫掺杂碳点（NClS/CDs）以及硒、氮、氯掺杂碳点（NClSe/CDs）。与未掺杂的CDs（0.66%）相比，这些NClS/CDs和NClSe/CDs的量子效率分别提高到了30.7%和42.9%。由于其更好的光吸收特性，NClS/CDs在532nm激光照射下能有效产生活性氧（ROS）用于光动力治疗（PDT）。考虑到NClS/CDs的ROS生成能力和表面载流子能力，我们设计通过硫酮连接子（TL）负载喜树碱（CPT）药物，得到载药效率为46.5%的h/CDs@CPT纳米囊泡（NVs）。在酸性环境中激光照射下，观察到ROS触发CPT释放，ROS敏感的TL分解后有50.2%的CPT释放。体外细胞研究表明，尽管在激光治疗下PDT具有高临床疗效且ROS诱导化疗反应，但h/CDs@CPT NVs对HeLa和4T1癌细胞的细胞毒性极小。HeLa和4T1细胞的共聚焦显微镜检查显示，h/CDs@CPT NVs产生红色发射图像用于潜在癌细胞检测。因此，我们的研究提出了一种基于h/CDs@CPT NVs的图像引导PDT和化疗平台，这将是未来癌症治疗的一个有吸引力的候选方案。
