Cargo loading within ferritin nanocages in preparation for tumor-targeted delivery

Jianlin Zhang, Dengfeng Cheng, Jiuyang He, Juanji Hong, Chang Yuan, Minmin Liang

Published: 2021-09-07 DOI: 10.1038/s41596-021-00602-5

Ferritin nanocages

Tumor-targeted delivery

Cargo loading

Anticancer drugs

Nanomedicines

AI 解读

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Ferritins are spherical iron storage proteins within cells, composed of 24subunits of two types, heavy-chain ferritin (HFn) and light-chain ferritin. Ferritins auto-assemble naturally into hollow nanocages with an outer diameter of 12 nm and an interior
Introduction
Materials
Additional materials required for Procedure 1
Additional materials required for Procedure 2
Additional materials required for Procedure 3
Additional materials required for Procedure 4
Procedure 1: preparation of metal oxide NPs within the HFn nanocage
Procedure 2: encapsulation of doxorubicin within HFn nanocage
Procedure 3: encapsulation of Gd3nobreak+nobreak within the HFn nanocage
Procedure 4: encapsulation of 64Cu2nobreak+nobreak radioisotope within the HFn nanocage
Troubleshooting
Timing
Anticipated results
- Reporting Summary
- References
References
ACKNOWLEDGMENTS

Kim, B. Y. S., Rutka, J. T. & Chan, W. C. W. Nanomedicine. N. Engl. J. Med. 363, 2434–2443 (2010).
Meel, R. et al. Smart cancer nanomedicine. Nat. Nanotechnol. 14, 1007–1017 (2019).
Harmsen, S., Wall, M. A., Huang, R. & Kircher, M. F. Cancer imaging using surface-enhanced resonance Raman scattering nanoparticles. Nat. Protoc. 12, 1400–1414 (2017).
Nam, J. et al. Cancer nanomedicine for combination cancer immunotherapy. Nat Rev. Mater. 4, 398–414 (2019).
Sanhai, W. R., Sakamoto, J. H., Canady, R. & Ferrari, M. Seven challenges for nanomedicine. Nat. Nanotechnol. 3, 242–244 (2008).
Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20–37 (2017).
Docter, D. et al. Quantitative profiling of the protein coronas that form around nanoparticles. Nat. Protoc. 9, 2030–2044 (2014).
Martin, J. D., Cabral, H., Stylianopoulos, T. & Jain, R. K. Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges. Nat. Rev. Clin. Oncol. 17, 251–266 (2020).
Zhang, J. et al. Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses. Sci. China Life Sci. 64, 352–362 (2021).
Harrison, P. M. & Arosio, P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim. Biophys. Acta 1275, 161–203 (1996).
Fan, K. et al. Magnetoferritin nanoparticles for targeting and visualizing tumour tissues. Nat. Nanotechnol. 7, 459–464 (2012).
Li, L. et al. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc. Natl Acad. Sci. USA 107, 3505–3510 (2010).
Zhen, Z. et al. RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. ACS Nano 7, 4830–4837 (2013).
Lin, X. et al. Hybrid ferritin nanoparticles as activatable probes for tumor imaging. Angew. Chem. Int. Ed. Engl. 50, 1569–1572 (2011).
Jutz, G. N. et al. Ferritin: a versatile building block for bionanotechnology. Chem. Rev. 115, 1653–1701 (2015).
Gao, F. et al. Hypoxia-tropic nanozymes as oxygen generators for tumor-favoring theranostics. Biomaterials. 230, 119635 (2020).
Provaznik, I., Vrba, R. & Kizek, R. Electrochemical behaviour of apoferritin encapsulating of silver (I) ions and its application for treatment of Staphylococcus aureus. Int. J. Electrochem. Sci. 7, 6378–6395 (2012).
Liang, M. et al. H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proc. Natl Acad. Sci. USA 111, 14900–14905 (2014).
Wang, T. et al. Bioengineered magnetoferritin nanozymes for pathological identification of high-risk and ruptured atherosclerotic plaques in humans. Nano Res. 12, 863–868 (2019).
Zhao, Y. et al. Bioengineered magnetoferritin nanoprobes for single-dose nuclear-magnetic resonance tumor imaging. ACS Nano 10, 4184–4191 (2016).
Li, Y. et al. Nanoparticle ferritin-bound erastin and rapamycin: a nanodrug combining autophagy and ferroptosis for anticancer therapy. Biomater. Sci. 7, 3779–3787 (2019).
Cheng, X. et al. TfR1 binding with H-ferritin nanocarrier achieves prognostic diagnosis and enhances the therapeutic efficacy in clinical gastric cancer. Cell Death Dis. 11, 1–13 (2020).
Macone, A. et al. Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells. Sci. Rep. 9, 11749 (2019).
Zhang, C., Zhang, X. & Zhao, G. Ferritin nanocage: a versatile nanocarrier utilized in the field of food, nutrition, and medicine. Nanomaterials (Basel) 10, 1894 (2020).
Tetter, S. & Hilvert, D. Enzyme encapsulation by a ferritin cage. Angew. Chem. Int. Ed. Engl. 56, 14933–14936 (2017).
Khoshnejad, M., Parhiz, H., Shuvaev, V. V., Dmochowski, I. J. & Muzykantov, V. R. Ferritin-based drug delivery systems: hybrid nanocarriers for vascular immunotargeting. J. Control. Release 282, 13–24 (2018).
Li, L. et al. Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells. Biomaterials 98, 143–151 (2016).
Wang, Z. et al. Metal ion assisted interface re-engineering of a ferritin nanocage for enhanced biofunctions and cancer therapy. Nanoscale 10, 1135–1144 (2018).
Uchida, M. et al. Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles. J. Am. Chem. Soc. 128, 16626–16633 (2006).
Truffi, M. et al. Ferritin nanocages: a biological platform for drug delivery, imaging and theranostics in cancer. Pharmacol. Res. 107, 57–65 (2016).
Wang, Z. et al. Functional ferritin nanoparticles for biomedical applications. Front. Chem. Sci. Eng. 11, 633–646 (2017).
Wang, Z. et al. Biomineralization-inspired synthesis of copper sulfide–ferritin nanocages as cancer theranostics. ACS Nano 10, 3453–3460 (2016).
Lin, X. et al. Chimeric ferritin nanocages for multiple function loading and multimodal imaging. Nano Lett. 11, 814–819 (2011).
Chauhan, V. P. et al. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat. Nanotechnol. 7, 383–388 (2012).
Huang, X. et al. Protein nanocages that penetrate airway mucus and tumor tissue. Proc. Natl Acad. Sci. USA 114, E6595–E6602 (2017).
Li, X. et al. Epidermal growth factor–ferritin H-chain protein nanoparticles for tumor active targeting. Small 8, 2505–2514 (2012).
Bitonto, V. et al. L-ferritin: a theranostic agent of natural origin for MRI visualization and treatment of breast cancer. J. Control. Release 319, 300–310 (2020).
Zhen, Z. et al. Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer. ACS Nano 7, 6988–6996 (2013).
Kuruppu, A. I. et al. An apoferritin-based drug delivery system for the tyrosine kinase inhibitor gefitinib. Adv. Healthc. Mater. 4, 2816–2821 (2015).
Zhou, H. et al. Mn-loaded apolactoferrin dots for in vivo MRI and NIR-II cancer imaging. J. Mater. Chem. C 7, 9448–9454 (2019).
Fan, J. et al. Direct evidence for catalase and peroxidase activities of ferritin–platinum nanoparticles. Biomaterials 32, 1611–1618 (2011).
Yang, Z. et al. Encapsulation of platinum anticancer drugs by apoferritin. Chem. Commun. (Camb) 33, 3453–3455 (2007).
Kim, M. et al. pH-dependent structures of ferritin and apoferritin in solution: disassembly and reassembly. Biomacromolecules 12, 1629–1640 (2011).
He, J., Fan, K. & Yan, X. Ferritin drug carrier (FDC) for tumor targeting therapy. J. Control Release 311, 288–300 (2019).
Tesarova, B., Musilek, K., Rex, S. & Heger, Z. Taking advantage of cellular uptake of ferritin nanocages for targeted drug delivery. J. Control Release 325, 176–190 (2020).
Liu, X. et al. Apoferritin–CeO 2 nano-truffle that has excellent artificial redox enzyme activity. Chem. Commun. (Camb) 48, 3155–3157 (2012).
Iwahori, K., Yoshizawa, K., Muraoka, M. & Yamashita, I. Fabrication of ZnSe nanoparticles in the apoferritin cavity by designing a slow chemical reaction system. Inorg. Chem. 44, 6393–6400 (2005).
Naito, M., Iwahori, K., Miura, A., Yamane, M. & Yamashita, I. Circularly polarized luminescent CdS quantum dots prepared in a protein nanocage. Angew. Chem. Int. Ed. Engl. 49, 7006–7009 (2010).
Yamashita, I., Hayashi, J. & Hara, M. Bio-template synthesis of uniform CdSe nanoparticles using cage-shaped protein, apoferritin. Chem. Lett. 33, 1158–1159 (2004).
Klem, M. T., Mosolf, J., Young, M. & Douglas, T. Photochemical mineralization of europium, titanium, and iron oxyhydroxide nanoparticles in the ferritin protein cage. Inorg. Chem. 47, 2237–2239 (2008).
Hosein, H.-A., Strongin, D. R., Allen, M. & Douglas, T. Iron and cobalt oxide and metallic nanoparticles prepared from ferritin. Langmuir. 20, 10283–10287 (2004).
Monti, D. M., Ferraro, G. & Merlino, A. Ferritin-based anticancer metallodrug delivery: crystallographic, analytical and cytotoxicity studies. Nanomedicine 20, 101997 (2019).
Falvo, E. et al. Antibody–drug conjugates: targeting melanoma with cisplatin encapsulated in protein-cage nanoparticles based on human ferritin. Nanoscale 5, 12278–12285 (2013).
Liu, W. et al. Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment. J. Control. Release 323, 191–202 (2020).
Liu, M., Zhu, Y., Wu, T., Cheng, J. & Liu, Y. Nanobody-ferritin conjugate for targeted photodynamic therapy. Chemistry 26, 7442–7450 (2020).
Lee, E. J. et al. Engineered proteinticles for targeted delivery of siRNA to cancer cells. Adv. Funct. Mater. 25, 1279–1286 (2015).
Wang, W. et al. Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy. Nanomedicine 16, 69–78 (2019).
Falvo, E. et al. The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity. J. Control. Release 275, 177–185 (2018).
Huang, P. et al. Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy. Adv. Mater. 26, 6401–6408 (2014).
Chen, L. et al. Encapsulation of β-carotene within ferritin nanocages greatly increases its water-solubility and thermal stability. Food Chem. 149, 307–312 (2014).
Huang, C. et al. Ultra-high loading of sinoporphyrin sodium in ferritin for single-wave motivated photothermal and photodynamic co-therapy. Biomater. Sci. 5, 1512–1516 (2017).
Li, K. et al. Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells. Nanoscale 4, 188–193 (2012).
Kim, H.-K. et al. Highly brain-permeable apoferritin nanocage with high dysprosium loading capacity as a new T2 contrast agent for ultra-high field magnetic resonance imaging. Biomaterials 243, 119939 (2020).
Crich, S. G. et al. Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe. Cancer Res. 66, 9196–9201 (2006).
Cai, Y., Wang, Y., Zhang, T. & Pan, Y. Gadolinium-labeled ferritin nanoparticles as T 1 contrast agents for magnetic resonance imaging of tumors. ACS Appl. Nano Mater. 3, 8771–8783 (2020).
Sánchez, P. et al. MRI relaxation properties of water-soluble apoferritin-encapsulated gadolinium oxide-hydroxide nanoparticles. Dalton Trans. 5, 800–804 (2009).
Liang, M. et al. Bioengineered H-ferritin nanocages for quantitative imaging of vulnerable plaques in atherosclerosis. ACS Nano 12, 9300–9308 (2018).
Jiang, B. et al. Biomineralization synthesis of the cobalt nanozyme in SP94-ferritin nanocages for prognostic diagnosis of hepatocellular carcinoma. ACS Appl. Mater. Interfaces 11, 9747–9755 (2019).
Butts, C. A. et al. Directing noble metal ion chemistry within a designed ferritin protein. Biochemistry 47, 12729–12739 (2008).
Iwahori, K., Takagi, R., Kishimoto, N. & Yamashita, I. A size controlled synthesis of CuS nano-particles in the protein cage, apoferritin. Mater. Lett. 65, 3245–3247 (2011).
Gálvez, N., Sánchez, P. & Domínguez-Vera, J. M. Preparation of Cu and CuFe Prussian Blue derivative nanoparticles using the apoferritin cavity as nanoreactor. Dalton Trans. 15, 2492–2494 (2005).
Gálvez, N. et al. Apoferritin-encapsulated Ni and Co superparamagnetic nanoparticles. J. Mater. Chem. 16, 2757–2761 (2006).
Kashanian, S., Tarighat, F. & Rafipour, R. Biomimetic synthesis of cobalt nanoparticle using apoferritin and its application in electrochemical reaction to detect glucose. New Biotechnol. 25, S376 (2009).
Kashanian, S., Tarighat, F. A., Rafipour, R. & Abbasi-Tarighat, M. Biomimetic synthesis and characterization of cobalt nanoparticles using apoferritin, and investigation of direct electron transfer of Co (NPs)–ferritin at modified glassy carbon electrode to design a novel nanobiosensor. Mol. Biol. Rep. 39, 8793–8802 (2012).
Warne, B., Kasyutich, O. I., Mayes, E. L., Wiggins, J. A. L. & Wong, K. K. W. Self assembled nanoparticulate Co: Pt for data storage applications. IEEE Trans. Magn. 36, 3009–3011 (2000).
Gálvez, N. et al. A bioinspired approach to the synthesis of bimetallic CoNi nanoparticles. Inorg. Chem. 49, 1705–1711 (2010).
Okuda, M., Iwahori, K., Yamashita, I. & Yoshimura, H. Fabrication of nickel and chromium nanoparticles using the protein cage of apoferritin. Biotechnol. Bioeng. 84, 187–194 (2003).
Polanams, J., Ray, A. D. & Watt, R. K. Nanophase iron phosphate, iron arsenate, iron vanadate, and iron molybdate minerals synthesized within the protein cage of ferritin. Inorg. Chem. 44, 3203–3209 (2005).
Shin, Y., Dohnalkova, A. & Lin, Y. Preparation of homogeneous gold–silver alloy nanoparticles using the apoferritin cavity as a nanoreactor. J. Phys. Chem. C 114, 5985–5989 (2010).
Sennuga, A., van Marwijk, J. & Whiteley, C. G. Multiple fold increase in activity of ferroxidase–apoferritin complex by silver and gold nanoparticles. Nanomedicine 9, 185–193 (2013).
Turyanska, L. et al. The biocompatibility of apoferritin-encapsulated PbS quantum dots. Small 5, 1738–1741 (2009).
Turyanska, L. et al. The differential effect of apoferritin-PbS nanocomposites on cell cycle progression in normal and cancerous cells. J. Mater. Chem. 22, 660–665 (2012).
Hennequin, B. et al. Aqueous near-infrared fluorescent composites based on apoferritin-encapsulated PbS quantum dots. Adv. Mater. 20, 3592–3596 (2008).
Du, D. et al. Nanoparticle-based immunosensor with apoferritin templated metallic phosphate label for quantification of phosphorylated acetylcholinesterase. Biosens. Bioelectron. 26, 3857–3863 (2011).
Wu, H. et al. Apoferritin-templated yttrium phosphate nanoparticle conjugates for radioimmunotherapy of cancers. J. Nanosci. Nanotechnol. 8, 2316–2322 (2008).
Wu, H., Engelhard, M. H., Wang, J., Fisher, D. R. & Lin, Y. Synthesis of lutetium phosphate–apoferritin core–shell nanoparticles for potential applications in radioimmunoimaging and radioimmunotherapy of cancers. J. Mater. Chem. 18, 1779–1783 (2008).
Li, M., Viravaidya, C. & Mann, S. J. S. Polymer-mediated synthesis of ferritin-encapsulated inorganic nanoparticles. Small 3, 1477–1481 (2007).
Zhang, W. et al. Prussian blue modified ferritin as peroxidase mimetics and its applications in biological detection. J. Nanosci. Nanotechnol. 13, 60–67 (2013).
Hainfeld, J. F. Uranium-loaded apoferritin with antibodies attached: molecular design for uranium neutron-capture therapy. Proc. Natl Acad. Sci. USA 89, 11064–11068 (1992).
Xing, R. et al. Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin. J. Inorg. Biochem. 103, 1039–1044 (2009).
Zhang, Q. et al. Inlaying radiosensitizer onto the polypeptide shell of drug-loaded ferritin for imaging and combinational chemo-radiotherapy. Theranostics 9, 2779–2790 (2019).
Kilic, M. A., Ozlu, E. & Calis, S. A novel protein-based anticancer drug encapsulating nanosphere: apoferritin-doxorubicin complex. J. Biomed. Nanotechnol. 8, 508–514 (2012).
Cutrin, J. C., Crich, S. G., Burghelea, D., Dastru, W. & Aime, S. Curcumin/Gd loaded apoferritin: a novel “theranostic” agent to prevent hepatocellular damage in toxic induced acute hepatitis. Mol. Pharm. 10, 2079–2085 (2013).
Lei, Y. et al. Targeted tumor delivery and controlled release of neuronal drugs with ferritin nanoparticles to regulate pancreatic cancer progression. J. Control. Release 232, 131–142 (2016).

Cargo loading within ferritin nanocages in preparation for tumor-targeted delivery

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