Abstract
Engineered nanocarriers have been widely developed for tumor theranostics. However, the delivery of imaging probes or therapeutic drugs to the tumor pre-formation site for early and accurate detection and therapy remains a major challenge. Here, by using tailor-functionalized human H-ferritin (HFn), we developed a triple-modality nanoprobe IRdye800-M-HFn and achieved the early imaging of tumor cells before the formation of solid tumor tissues. Then, we developed an HFn-doxorubicin (Dox) drug delivery system by loading Dox into the HFn protein cage and achieved early-stage tumor therapy. The intravenous injection of HFn nanoprobes enabled the imaging of tumor cells as early as two days after tumor implantation, and the triple-modality imaging techniques, namely, near-infrared fluorescence molecular imaging (NIR-FMI), magnetic resonance imaging (MRI), and photoacoustic imaging (PAI), ensured the accuracy of detection. Further exploration indicated that HFn could specifically penetrate into pre-solid tumor sites by tumor-associated inflammation-mediated blood vessel leakage, followed by effective accumulation in tumor cells by the specific targeting property of HFn to transferrin receptor 1. Thus, the HFn-Dox drug delivery system delivered Dox into the tumor pre-formation site and effectively killed tumor cells at early stage. IRDye800-M-HFn nanoprobes and HFn-Dox provide promising strategies for early-stage tumor diagnosis and constructive implications for early-stage tumor treatment.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (31900981, 62027901, and 32000996), the Strategic Priority Research Program of CAS (XDB29040101), CAS Inter-disciplinary Innovation Team (JCTD-2020-08), Chinese Academy of Sciences (YJKYYQ20180048), the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC013), the National Key Research and Development Program of China (2017YFA0205501, 2017YFA0205200), Youth Innovation Promotion Association of Chinese Academy of Sciences (2019093), China Postdoctoral Science Foundation (2020M682358), the China Postdoctoral Science Special Foundation (2020TQ0280), the Grant for International Joint Research Project of the Institute of Medical Science, the University of Tokyo (Extension-2019-K3005), the Beijing-Tianjin-Hebei Basic Research Cooperation Special Program (19JCZDJC65300), and the CAS Key Laboratory of Mental Health Grant (KLMH2020K02). We thank Dr.s Xiaojun Huang and Gang Ji for their excellent technical support in cryo-EM imaging at the Transmission EM Facilities, Center for Biological Imaging, Institute of Biophysics. We also thank Jingnan Liang for technical support in TEM imaging at the Core Facility of Equipment, Institute of Microbiology. We thank Prof.s Shuaidong Huo and João Conde for their beneficial discussions and comments on our manuscript.
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Jiang, B., Jia, X., Ji, T. et al. Ferritin nanocages for early theranostics of tumors via inflammation-enhanced active targeting. Sci. China Life Sci. 65, 328–340 (2022). https://doi.org/10.1007/s11427-021-1976-0
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DOI: https://doi.org/10.1007/s11427-021-1976-0