title: H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection.
abstract: An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox-loaded HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration than free Dox and significantly inhibited tumor growth after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery.
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Minmin
authors.initials: M
authors.lastname: Liang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Kelong
authors.initials: K
authors.lastname: Fan
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Demin
authors.initials: D
authors.lastname: Duan
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Dongling
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceutical, National Laboratory of Biomacromolecules, Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; and yanxy@ibp.ac.cn.
authors.forename: Xiyun
authors.initials: X
authors.lastname: Yan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001052:Apoferritins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007267:Injections; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D001052:Apoferritins