H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [115]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cancer nanotechnology: opportunities and challenges
Ferrari, M. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1566 · Cited by 4,558 · see citing works
Delivering nanomedicine to solid tumors
Jain, R. K., & Stylianopoulos, T. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.139 · Cited by 3,196 · see citing works
The ferritins: molecular properties, iron storage function and cellular regulation
Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667 · see citing works
Paul Ehrlich's magic bullet concept: 100 years of progress
Strebhardt, K., & Ullrich, A. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2394 · Cited by 1,461 · see citing works
FERRITIN: STRUCTURE, GENE REGULATION, AND CELLULAR FUNCTION IN ANIMALS, PLANTS, AND MICROORGANISMS
Theil, E. C. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.001445 · Cited by 1,337 · see citing works
Chauhan, V. P., Stylianopoulos, T., Martin, J. D., Popović, Z., Chen, O., Kamoun, W. S., Bawendi, M. G., Fukumura, D., & Jain, R. K. (2012) · Nature Nanotechnology · doi:10.1038/nnano.2012.45 · Cited by 1,101 · see citing works
Ferritins: A family of molecules for iron storage, antioxidation and more
Arosio, P., Ingrassia, R., & Cavadini, P. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.09.004 · Cited by 886 · see citing works
Strategies for advancing cancer nanomedicine
Chauhan, V. P., & Jain, R. K. (2013) · Nature Materials · doi:10.1038/nmat3792 · Cited by 815 · see citing works
New Technologies for Human Cancer Imaging
Frangioni, J. V. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.3065 · Cited by 800 · see citing works
Magnetoferritin nanoparticles for targeting and visualizing tumour tissues
Fan, K., Cao, C., Pan, Y., Lü, D., Yang, D., Feng, J., Song, L., Liang, M., & Yan, X. (2012) · Nature Nanotechnology · doi:10.1038/nnano.2012.90 · Cited by 756 · see citing works
Self-citationPrecise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers
Gu, F., Zhang, L., Teply, B. A., Mann, N., Wang, A. Z., Radovic‐Moreno, A. F., Langer, R., & Farokhzad, O. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711714105 · Cited by 714 · see citing works
Magnetoferritin: in Vitro Synthesis of a Novel Magnetic Protein
Meldrum, F. C., Heywood, B. R., & Mann, S. (1992) · Science · doi:10.1126/science.1636086 · Cited by 572 · see citing works
Binding and uptake of H-ferritin are mediated by human transferrin receptor-1
Li, L., Fang, C. J., Ryan, J. C., Niemi, E. C., Lebrón, J. A., Björkman, P. J., Arase, H., Torti, F. M., Torti, S. V., Nakamura, M. C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913192107 · Cited by 558 · see citing works
Targeting kidney mesangium by nanoparticles of defined size
Choi, C. H. J., Zuckerman, J. E., Webster, P. C., & Davis, M. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103573108 · Cited by 503 · see citing works
Self-Assembled Targeted Nanoparticles: Evolution of Technologies and Bench to Bedside Translation
Shi, J., Xiao, Z., Kamaly, N., & Farokhzad, O. C. (2011) · Accounts of Chemical Research · doi:10.1021/ar200054n · Cited by 476 · see citing works
Targeting of Cancer Cells with Ferrimagnetic Ferritin Cage Nanoparticles
Uchida, M., Flenniken, M. L., Allen, M., Willits, D. A., Crowley, B. E., Brumfield, S. K., Willis, A. F., Jackiw, L. O., Jutila, M. A., Young, M., et al. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0655690 · Cited by 395 · see citing works
RGD-Modified Apoferritin Nanoparticles for Efficient Drug Delivery to Tumors
Zhen, Z., Tang, W., Chen, H., Lin, X., Todd, T., Wang, G., Cowger, T. A., Chen, X. S., & Xie, J. (2013) · ACS Nano · doi:10.1021/nn305791q · Cited by 368 · see citing works
pH-Dependent Structures of Ferritin and Apoferritin in Solution: Disassembly and Reassembly
Kim, M., Rho, Y., Jin, K. S., Ahn, B., Jung, S., Kim, H., & Ree, M. (2011) · Biomacromolecules · doi:10.1021/bm200026v · Cited by 309 · see citing works
Predicting the course of Gompertzian growth
Norton, L., Simon, R. M., Brereton, H. D., & Bogdén, A. E. (1976) · Nature · doi:10.1038/264542a0 · Cited by 308 · see citing works
Biomimetic synthesis of cadmium sulfide‐ferritin nanocomposites
Wong, K. K. W., & Mann, S. (1996) · Advanced Materials · doi:10.1002/adma.19960081114 · Cited by 278 · see citing works
Zhen, Z., Tang, W., Guo, C., Chen, H., Lin, X., Liu, G., Fei, B., Chen, X. S., Xu, B., & Xie, J. (2013) · ACS Nano · doi:10.1021/nn402199g · Cited by 273 · see citing works
Chimeric Ferritin Nanocages for Multiple Function Loading and Multimodal Imaging
Lin, X., Xie, J., Niu, G., Zhang, F., Gao, H., Yang, M., Quan, Q., Aronova, M. A., Zhang, G., Lee, S., et al. (2011) · Nano Letters · doi:10.1021/nl104141g · Cited by 263 · see citing works
Encapsulation of platinum anticancer drugs by apoferritin
Yang, Z., Wang, X., Diao, H., et al. (2007) · Chemical Communications · doi:10.1039/b705326f · Cited by 225 · see citing works
Discovery and development of anthracycline antitumour antibiotics
Lown, J. W. (1993) · Chemical Society Reviews · doi:10.1039/cs9932200165 · Cited by 166 · see citing works
Falvo, E., Tremante, E., Fraioli, R., Leonetti, C., Zamparelli, C., Boffi, A., Morea, V., Ceci, P., & Giacomini, P. (2013) · Nanoscale · doi:10.1039/c3nr04268e · Cited by 155 · see citing works
Hainfeld, J. F. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.11064 · Cited by 122 · see citing works
Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin
Xing, R., Wang, X., Zhang, C., Zhang, Y., Wang, Q., Yang, Z., & Guo, Z. (2009) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2009.05.001 · Cited by 117 · see citing works
Ramanathan, K., Pandey, S. S., Kumar, R., Gulati, A., Murthy, A. S. N., & Malhotra, B. D. (2000) · Journal of Applied Polymer Science · doi:10.1002/1097-4628(20001017)78:3 · Cited by 108 · see citing works
Klem, M. T., Mosolf, J., Young, M., & Douglas, T. (2008) · Inorganic Chemistry · doi:10.1021/ic701740q · Cited by 89 · see citing works
Epidermal Growth Factor–Ferritin H‐Chain Protein Nanoparticles for Tumor Active Targeting
Li, X., Qiu, L., Zhu, P. H., et al. (2012) · Small · doi:10.1002/smll.201200066 · Cited by 81 · see citing works
Immunological tolerance and autoimmunity
Romagnani, S. (2006) · Internal and Emergency Medicine · doi:10.1007/bf02934736 · Cited by 80 · see citing works
Jeon, J. O., Kim, S., Choi, E., Shin, K., Cha, K., So, I.-S., Kim, S.-J., Jun, E., Kim, D., Ahn, H. J., et al. (2013) · ACS Nano · doi:10.1021/nn403184u · Cited by 80 · see citing works
Cutrìn, J. C., Crich, S. G., Burghelea, D., et al. (2013) · Molecular Pharmaceutics · doi:10.1021/mp3006177 · Cited by 69 · see citing works
Taneichi, M., Ishida, H., Kajino, K., Ogasawara, K., Tanaka, Y., Kasai, M., Mori, M., Nishida, M., Yamamura, H., Mizuguchi, J., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2324 · Cited by 66 · see citing works
Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells
Li, K., Zhang, Z., Luo, M., et al. (2011) · Nanoscale · doi:10.1039/c1nr11132a · Cited by 66 · see citing works
Iron(III) complexation of Desferrioxamine B encapsulated in apoferritin
Dominguez-Vera, J. M. (2004) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2003.12.015 · Cited by 61 · see citing works
Yan, F., Zhang, Y., Kim, K. S., et al. (2010) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2009.00696.x · Cited by 55 · see citing works
Identification of a fluorescent general anesthetic, 1-aminoanthracene
Butts, C. A., Jin, X., Brannigan, G. H., Saad, A. A., Venkatachalan, S. P., Pearce, R. A., Klein, M. L., Eckenhoff, R. G., & Dmochowski, I. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810590106 · Cited by 51 · see citing works
Siddik, Z. H. (2005) · The Cancer Handbook · doi:10.1002/0470025077.chap84b · Cited by 47 · see citing works
Crystal structure of vinblastine
Bau, R., & Jin, K. K. (2000) · Journal of the Chemical Society Perkin Transactions 1 · doi:10.1039/b001855o · Cited by 25 · see citing works
Salvador-Morales, C. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/398 · Cited by 19 · see citing works
Langer, R. (2012) · Frontiers in Bioscience-Elite · doi:10.2741/e398 · Cited by 19 · see citing works
Magnetizable antibody‐like proteins
Dehal, P. K., Livingston, C. F., Dunn, C. G., et al. (2010) · Biotechnology Journal · doi:10.1002/biot.200900273 · Cited by 13 · see citing works
Tan, H., Jiang, L., Gu, Y., et al. (2013) · Annals of Nuclear Medicine · doi:10.1007/s12149-013-0776-7 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 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]
Cited by
Sorted by citations
Ligand-installed nanocarriers toward precision therapy
Mi, P., Cabral, H., & Kataoka, K. (2020) · Advanced Materials · doi:10.1002/adma.201902604 · Cited by 350 · see citing works
Iron as a central player and promising target in cancer progression
Jung, M., Mertens, C., Tomat, E., & Brüne, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020273 · Cited by 268 · see citing works
“FT nanocages are used to encapsulate chemotherapeutic agents such as doxorubicin [115] or gold ions to induce tumor cell death [116].”
BackgroundProtein nanocages that penetrate airway mucus and tumor tissue
Huang, X., Chisholm, J., Zhuang, J., Xiao, Y., Duncan, G., Chen, X., Suk, J. S., & Hanes, J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705407114 · Cited by 131 · see citing works
Cheng, Q., Du, L., Meng, L., Han, S., Wei, T., Wang, X., Wu, Y., Song, X., Zhou, J., Zheng, S., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b11789 · Cited by 85 · see citing works
Cai, Y., Deng, T., Pan, Y., & Zink, J. I. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202002043 · Cited by 48 · see citing works
- 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
- Publisher
- National Academy of Sciences
- Published
- 2014-09-29
- Volume
- 111
- Issue
- 41
- Pages
- 14900-14905
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4205604
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review