Nanozyme Medical Center, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Sci China Life Sci. 2022 Feb;65(2):328-340. doi: 10.1007/s11427-021-1976-0. Epub 2021 Aug 31.
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.
工程化纳米载体已广泛用于肿瘤诊治。然而，将成像探针或治疗药物递送至肿瘤前形成部位以进行早期和准确的检测和治疗仍然是一个主要挑战。在这里，我们通过使用定制功能化的人铁蛋白（HFn），开发了一种三模态纳米探针 IRdye800-M-HFn，并实现了在实体瘤组织形成之前对肿瘤细胞的早期成像。然后，我们通过将阿霉素（Dox）载入 HFn 蛋白笼中开发了一种 HFn-Dox 药物递送系统，并实现了早期肿瘤治疗。HFn 纳米探针的静脉注射可在肿瘤植入后两天内即可对肿瘤细胞进行成像，并且近红外荧光分子成像（NIR-FMI）、磁共振成像（MRI）和光声成像（PAI）等三模态成像技术可确保检测的准确性。进一步的探索表明，HFn 可以通过肿瘤相关炎症介导的血管渗漏特异性穿透到预实体瘤部位，然后通过 HFn 对转铁蛋白受体 1 的特异性靶向特性有效地将 Dox 递送至肿瘤细胞。因此，HFn-Dox 药物递送系统将 Dox 递送至肿瘤前形成部位，并有效地在早期杀死肿瘤细胞。IRDye800-M-HFn 纳米探针和 HFn-Dox 为早期肿瘤诊断提供了有前途的策略，并对早期肿瘤治疗具有建设性意义。
