Cited by 507Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsRNA Interference and Gene Delivery

H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

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Liang, Minmin, Fan, Kelong, Zhou, Meng, Duan, Demin, Zheng, Jiyan, Yang, Dongling, Feng, Jing, Yan, Xiyun·2014·Proceedings of the National Academy of Sciences

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.

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  • FT nanocages are used to encapsulate chemotherapeutic agents such as doxorubicin or gold ions to induce tumor cell death.

    “FT nanocages are used to encapsulate chemotherapeutic agents such as doxorubicin [115] or gold ions to induce tumor cell death [116].”

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  1. [31]Yang SC, Ge HX, Hu Y, Jiang XQ, Yang CZ. Doxorubicin-loaded poly(butylcyanoacrylate) nanoparticles produced by emulsifier-free emulsion polymerization. J Appl Polym Sci. 2000;78(3):517–526. [Google Scholar]

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Authors
Liang, M., Fan, K., Zhou, M., Duan, D., Zheng, J., Yang, D., Feng, J., & Yan, X.
Affiliations
Chinese Academy of Sciences (CN)
Venue
Proceedings of the National Academy of Sciences
Published
2014-09-29
Volume
111
Issue
41
Pages
14900-14905
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2081845177
Cited by
507
References
44
Citations by year
2026: 26 · 2025: 57 · 2024: 46 · 2023: 45 · 2022: 42 · 2021: 66 · 2020: 49 · 2019: 50 · 2018: 36 · 2017: 38 · 2016: 38 · 2015: 12 · 2014: 1
FWCI
11.22
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
H-ferritin, doxorubicin, nanocages, drug delivery, transferrin receptor 1, tumor targeting, lysosomal drug release, intratumoral drug concentration, single injection, anticancer nanocarriers, biocompatibility, maximum tolerated dose
MeSH terms
Animals, Antineoplastic Agents, Apoferritins, Dose-Response Relationship, Drug, Doxorubicin, Endocytosis, Female, Humans, Injections, Mice, Inbred BALB C, Mice, Nude, Neoplasms, Tissue Distribution, HT29 Cells, Xenograft Model Antitumor Assays, Nanoparticles

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