Ferritin nanocages for early theranostics of tumors via inflammation-enhanced active targeting

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.