Protein nanoparticles in molecular, cellular, and tissue imaging

Overview

Tanvi Sushil Kaku, Sierin Lim

Published Online: Apr 06 2021

DOI: 10.1002/wnan.1714

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Abstract The quest to develop ideal nanoparticles capable of molecular, cellular, and tissue level imaging is ongoing. Since certain imaging probes and nanoparticles face drawbacks such as low aqueous solubility, increased ROS generation leading to DNA damage, apoptosis, and high cellular/organ toxicities, the development of versatile and biocompatible nanocarriers becomes necessary. Protein nanoparticles (PNPs) are one such promising class of nanocarriers that possess most of the desirable properties of an ideal nanocarrier for bioimaging applications. PNPs demonstrate high aqueous solubility, minimal cytotoxicity, and multi‐cargo loading capacity. They are also amenable to surface‐functionalization, as well as modulation of their hydrophobicity and hydrophilicity. The use of PNPs for bioimaging applications has made rapid advancements in the past two decades. Being comparatively less explored, the field opens up a plethora of opportunities and focus areas to engineer ideal bioimaging protein nanocarriers. The use of PNPs as carriers of their natural ligands as well as other heavy metals and fluorescent probes, along with drug molecules for combined theranostic applications has been reported. In addition, surface functionalization to impart specificity of targeting the PNPs has been shown to reduce nonspecific cellular interactions, thus reducing systemic toxicity. PNPs have been explored for their application in imaging of numerous cancers, cardiovascular diseases as well as imaging of the brain using near infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), X‐ray computed tomography (CT), positron emission tomography (PET), single‐photon emission computed tomography (SPECT), ultrasound (US), and photoacoustic (PA) imaging. This article is categorized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Use of protein nanoparticles (PNPs) for MR, NIRF, CT, SPECT, PET, and US imaging. PNPs have been used as multifunctional nanocarriers and can be employed for simultaneous bioimaging and drug delivery for a wide range of imaging modalities. The property of surface functionalization enables the PNPs to be used for specific targeting. SELF indicates targeting of natural receptors (e.g., transferrin) using unmodified PNP (e.g., ferritin) surface

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Representative images of various imaging applications of PNPs using multiple imaging modalities. (a) The 3D PAI of U87MG glioblastoma tumor, preinjection and postinjection of CuS‐Fn (top); PET images of tumor bearing mice post 50 μCi ⁶⁴CuS‐Fn nanocage i.v. injection, after 2, 4, 8, 20, and 24 h (bottom). Adapted with permission from Wang et al. (2016). Copyright (2016) American Chemical Society; (b) In vivo MRI of Gd(III)‐DTPA and Hsp 16.5 4‐Nanocage conjugated to gadolinium(III)‐chelated contrast agents measured with 9.4 T MRI. The 4‐Nanocage showed selective and high contrast enhancement of tumor regions represented by red dashed circles. Adapted with permission from Kawano et al. (2018). Copyright (2018), with permission from Elsevier; (c) GV enhancement of transcranial functional ultrasound signals. Activation maps overlaid on power Doppler images of the mouse brain with and without bolus injection of saline, microbubbles, and GVs, respectively, have been represented in the figure. Adapted with permission from Maresca et al. (2020), from Elsevier; (d) SPECT–CT images of wild type and Apoe^−/− mice using ^99mTc‐HFn over a period of 12, 20, and 33 weeks. The red circles indicate atherosclerotic (AS) plaques. Adapted with permission from Liang et al. (2018). Copyright (2018) American Chemical Society; (e) in vivo NIRF imaging measured in real‐time post i.v. injection of Alexa Fluor 750‐labeled HspG41C‐CTT nanocages in HT1080 and HT29 (negative control) tumor‐bearing mice. The dotted squares indicate solid tumor growths of subcutaneously injected cancer cells. Adapted with permission from Kawano et al. (2015)

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Transmission electron microscope images of (a) ironfree ferritin nanocages. Adapted with permission from Wang et al. (2016); Copyright (2016) American Chemical Society; (b) VLP‐QDs assembled from wild type VP1 protein and quantum dots. Adapted with permission from Sun et al. (2016). Copyright (2016) American Chemical Society; (c) HspG41C PNPs where the white arrowheads point to the nanocages. Adapted with permission from Kawano et al. (2014). Systemic delivery of protein nanocages bearing CTT peptides for enhanced imaging of MMP‐2 expression in metastatic tumor models, open access); (d) structure of GVs from Anabaena flos‐aquae in its intact form, and (e) in its collapsed form, used for ultrasound contrast. The part figures (d,e) have been adapted with permission from Lakshmanan et al. (2017). Copyright (2017) Springer Nature. Scale bars are (a) 100 nm, (b) 50 nm, (c) 20 nm, (d) 200 nm, and (e) 200 nm

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Crystal structures of PNP representatives (downloaded from RCSB PDB and displayed using PyMOL). (a) Human H chain ferritin (PDB ID 2FHA) (Hempstead et al., 1997). (b) A small heat shock protein from Methanococcus jannaschii (PDB ID 1SHS) (Kim et al., 1998). (c) A closed form of the Archaeoglobus fulgidus ferritin obtained by site directed mutagenesis (PDB ID 3KX9) (Sana et al., 2013). (d) Horse spleen apoferritin (PDB ID 2W0O) (de Val et al., 2012). (e) Structure of free SV40 VP1 pentamer (PDB ID 3BWQ) (Neu et al., 2008). And (f) crystal structures of a novel open pore ferritin from the hyperthermophilic archaeon Archaeoglobus fulgidus (PDB ID 1SQ3) (Johnson et al., 2005). These images were created using PyMOL 2.4 (The PyMOL Molecular Graphics System, Version 2.4.1 Schrödinger, LLC). The α helices, β sheets, and loops have been represented in blue, gray, and red colors, respectively

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References

Ahmed,, G. H. G., Laíño,, R. B., Calzón,, J. A. G., & García,, M. E. D. (2016). Facile synthesis of water‐soluble carbon nano‐onions under alkaline conditions. Beilstein Journal of Nanotechnology, 7(1), 758–766. https://doi.org/10.3762/bjnano.7.67
Alekseenko,, A. V., Waseem,, T. V., & Fedorovich,, S. V. (2008). Ferritin, a protein containing iron nanoparticles, induces reactive oxygen species formation and inhibits glutamate uptake in rat brain synaptosomes. Brain Research, 1241(5), 193–200. https://doi.org/10.1016/j.brainres.2008.09.012
Ali,, H., Ghosh,, S., & Jana,, N. R. (2018). Biomolecule‐derived fluorescent carbon nanoparticle as bioimaging probe. MRS Advances, 3(15), 779–788. https://doi.org/10.1557/adv.2018.80
Atukorale,, P. U., Covarrubias,, G., Bauer,, L., & Karathanasis,, E. (2017). Vascular targeting of nanoparticles for molecular imaging of diseased endothelium. Advanced Drug Delivery Reviews, 113, 141–156. https://doi.org/10.1016/j.addr.2016.09.006
Awaad,, A., Nakamura,, M., & Ishimura,, K. (2012). Imaging of size‐dependent uptake and identification of novel pathways in mouse Peyer`s patches using fluorescent organosilica particles. Nanomedicine: Nanotechnology, Biology, and Medicine, 8(5), 627–636. https://doi.org/10.1016/j.nano.2011.08.009
Baldelomar,, E. J., Charlton,, J. R., DeRonde,, K. A., & Bennett,, K. M. (2019). In vivo measurements of kidney glomerular number and size in healthy and Os/+ mice using MRI. American Journal of Physiology: Renal Physiology, 317(4), F865–F873. https://doi.org/10.1152/ajprenal.00078.2019
Bhaskar,, S., & Lim,, S. (2017). Engineering protein nanocages as carriers for biomedical applications. NPG Asia Materials, 9(4), 1–18. https://doi.org/10.1038/am.2016.128
Bhushan,, B., Kumar,, S. U., Matai,, I., Sachdev,, A., Dubey,, P., & Gopinath,, P. (2014). Ferritin nanocages: A novel platform for biomedical applications. Journal of Biomedical Nanotechnology, 10(10), 2950–2976. https://doi.org/10.1166/jbn.2014.1980
Bitonto,, V., Alberti,, D., Ruiu,, R., Aime,, S., Geninatti Crich,, S., & Cutrin,, J. C. (2020). L‐ferritin: A theranostic agent of natural origin for MRI visualization and treatment of breast cancer. Journal of Controlled Release, 319, 300–310. https://doi.org/10.1016/j.jconrel.2019.12.051
Blanco,, E., Shen,, H., & Ferrari,, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941–951. https://doi.org/10.1038/nbt.3330
Borden,, M., & Sirsi,, S. (2014). Ultrasound imaging: Better contrast with vesicles. Nature Nanotechnology, 9(4), 248–249. https://doi.org/10.1038/nnano.2014.68
Bulte,, J. W. M. (2018). Gas vesicles as collapsible MRI contrast agents. Nature Materials, 17(5), 386–387. https://doi.org/10.1038/s41563-018-0073-x
Cabral,, H., Matsumoto,, Y., Mizuno,, K., Chen,, Q., Murakami,, M., Kimura,, M., Terada,, Y., Kano,, M. R., Miyazono,, K., Uesaka,, M., Nishiyama,, N., & Kataoka,, K. (2011). Accumulation of sub‐100 nm polymeric micelles in poorly permeable tumours depends on size. Nature Nanotechnology, 6(12), 815–823. https://doi.org/10.1038/nnano.2011.166
Cai,, Y., Cao,, C., He,, X., Yang,, C., Tian,, L., Zhu,, R., & Pan,, Y. (2015). Enhanced magnetic resonance imaging and staining of cancer cells using ferrimagnetic H‐ferritin nanoparticles with increasing core size. International Journal of Nanomedicine, 10, 2619–2634. https://doi.org/10.2147/IJN.S80025
Camisasca,, A., & Giordani,, S. (2017). Carbon nano‐onions in biomedical applications: Promising theranostic agents. Inorganica Chimica Acta, 468, 67–76. https://doi.org/10.1016/j.ica.2017.06.009
Cao,, L., Wang,, X., Meziani,, M. J., Lu,, F., Wang,, H., Luo,, P. G., Lin,, Y., Harruff,, B. A., Veca,, L. M., Murray,, D., Xie,, S. Y., & Sun,, Y. P. (2007). Carbon dots for multiphoton bioimaging. Journal of the American Chemical Society, 129(37), 11318–11319. https://doi.org/10.1021/ja073527l
Chen,, H., Qin,, Z., Zhao,, J., He,, Y., Ren,, E., Zhu,, Y., Liu,, G., Mao,, C., & Zheng,, L. (2019). Cartilage‐targeting and dual MMP‐13/pH responsive theranostic nanoprobes for osteoarthritis imaging and precision therapy. Biomaterials, 225, 119520. https://doi.org/10.1016/j.biomaterials.2019.119520
Chen,, Z., Zhai,, M., Xie,, X., Zhang,, Y., Ma,, S., Li,, Z., Yu,, F., Zhao,, B., Zhang,, M., Yang,, Y., & Mei,, X. (2017). Apoferritin nanocage for brain targeted doxorubicin delivery. Molecular Pharmaceutics, 14(9), 3087–3097. https://doi.org/10.1021/acs.molpharmaceut.7b00341
Cherin,, E., Melis,, J. M., Bourdeau,, R. W., Yin,, M., Kochmann,, D. M., Foster,, F. S., & Shapiro,, M. G. (2017). Acoustic behavior of Halobacterium salinarum gas vesicles in the high‐frequency range: Experiments and modeling. Ultrasound in Medicine and Biology, 43(5), 1016–1030. https://doi.org/10.1016/j.ultrasmedbio.2016.12.020
Conti,, L., Lanzardo,, S., Ruiu,, R., Cadenazzi,, M., Cavallo,, F., Aime,, S., & Crich,, S. G. (2016). L‐ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents. Oncotarget, 7(41), 66713–66727. https://doi.org/10.18632/oncotarget.10920
Cui,, D., Tian,, F., Ozkan,, C. S., Wang,, M., & Gao,, H. (2005). Effect of single wall carbon nanotubes on human HEK293 cells. Toxicology Letters, 155(1), 73–85. https://doi.org/10.1016/j.toxlet.2004.08.015
Cutrin,, J. C., Crich,, S. G., Burghelea,, D., Dastrù,, W., & Aime,, S. (2013). Curcumin/Gd loaded apoferritin: A novel “theranostic” agent to prevent hepatocellular damage in toxic induced acute hepatitis. Molecular Pharmaceutics, 10(5), 2079–2085. https://doi.org/10.1021/mp3006177
De Val,, N., Declercq,, J. P., Lim,, C. K., & Crichton,, R. R. (2012). Structural analysis of haemin demetallation by L‐chain apoferritins. Journal of Inorganic Biochemistry, 112, 77–84. https://doi.org/10.1016/j.jinorgbio.2012.02.031
Derfus,, A. M., Chan,, W. C. W., & Bhatia,, S. N. (2004). Intracellular delivery of quantum dots for live cell labeling and organelle tracking. Advanced Materials, 16(12), 961–966. https://doi.org/10.1002/adma.200306111
Diaz,, D., Care,, A., & Sunna,, A. (2018). Bioengineering strategies for protein‐based nanoparticles. Genes, 9(7), 370. https://doi.org/10.3390/genes9070370
Du,, Y., & Guo,, S. (2016). Chemically doped fluorescent carbon and graphene quantum dots for bioimaging, sensor, catalytic and photoelectronic applications. Nanoscale, 8(5), 2532–2543. https://doi.org/10.1039/C5NR07579C
Escobedo,, J. O., Rusin,, O., Lim,, S., & Strongin,, R. M. (2010). NIR dyes for bioimaging applications. Current Opinion in Chemical Biology, 14(1), 64–70. https://doi.org/10.1016/j.cbpa.2009.10.022
Flenniken,, M. L., Willits,, D. A., Harmsen,, A. L., Liepold,, L. O., Harmsen,, A. G., Young,, M. J., & Douglas,, T. (2006). Melanoma and lymphocyte cell‐specific targeting incorporated into a heat shock protein cage architecture. Chemistry and Biology, 13(2), 161–170. https://doi.org/10.1016/j.chembiol.2005.11.007
Frey,, N. A., Peng,, S., Cheng,, K., & Sun,, S. (2009). Magnetic nanoparticles: Synthesis, functionalization, and applications in bioimaging and magnetic energy storage. Chemical Society Reviews, 38(9), 2532–2542. https://doi.org/10.1039/b815548h
Geninatti Crich,, S., Bussolati,, B., Tei,, L., Grange,, C., Esposito,, G., Lanzardo,, S., Camussi,, G., & Aime,, S. (2006). Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium‐loaded apoferritin probe. Cancer Research, 66(18), 9196–9201. https://doi.org/10.1158/0008-5472.CAN-06-1728
Geninatti Crich,, S., Cadenazzi,, M., Lanzardo,, S., Conti,, L., Ruiu,, R., Alberti,, D., Cavallo,, F., Cutrin,, J. C., & Aime,, S. (2015). Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells. Nanoscale, 7(15), 6527–6533. https://doi.org/10.1039/c5nr00352k
Geninatti Crich,, S., Cutrin,, J. C., Lanzardo,, S., Conti,, L., Kálmán,, F. K., Szabó,, I., Iolascon,, A., & Aime,, S. (2012). Mn‐loaded apoferritin: A highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model. Contrast Media and Molecular Imaging, 7(3), 281–288. https://doi.org/10.1002/cmmi.492
Ghosh,, M., Sonkar,, S. K., Saxena,, M., & Sarkar,, S. (2011). Carbon nano‐onions for imaging the life cycle of Drosophila melanogaster. Small, 7(22), 3170–3177. https://doi.org/10.1002/smll.201101158
González‐Béjar,, M., Francés‐Soriano,, L., & Pérez‐Prieto,, J. (2016). Upconversion nanoparticles for bioimaging and regenerative medicine. Frontiers in Bioengineering and Biotechnology, 4, 47. https://doi.org/10.3389/fbioe.2016.00047
Hahn,, M. A., Singh,, A. K., Sharma,, P., Brown,, S. C., & Moudgil,, B. M. (2011). Nanoparticles as contrast agents for in‐vivo bioimaging: Current status and future perspectives. Analytical and Bioanalytical Chemistry, 399(1), 3–27. https://doi.org/10.1007/s00216-010-4207-5
Hasebroock,, K. M., & Serkova,, N. J. (2009). Toxicity of MRI and CT contrast agents. Expert Opinion on Drug Metabolism and Toxicology, 5(4), 403–416. https://doi.org/10.1517/17425250902873796
He,, W., Ai,, K., & Lu,, L. (2015). Nanoparticulate X‐ray CT contrast agents. Science China Chemistry, 58(5), 753–760. https://doi.org/10.1007/s11426-015-5351-8
Hemmilä,, I., & Laitala,, V. (2005). Progress in lanthanides as luminescent probes. Journal of Fluorescence, 15(4), 529–542. https://doi.org/10.1007/s10895-005-2826-6
Hempstead,, P. D., Yewdall,, S. J., Fernie,, A. R., Lawson,, D. M., Artymiuk,, P. J., Rice,, D. W., Ford,, G. C., & Harrison,, P. M. (1997). Comparison of the three‐dimensional structures of recombinant human H and horse L ferritins at high resolution. Journal of Molecular Biology, 268(2), 424–448. https://doi.org/10.1006/jmbi.1997.0970
Hrvoje,, L., & Greenstaff,, M. W. (2014). X‐ray computed tomography contrast agents. Chemical Reviews, 113(3), 1641–1666. https://doi.org/10.1021/cr200358s
Huang,, P., Rong,, P., Jin,, A., Yan,, X., Zhang,, M. G., Lin,, J., Hu,, H., Wang,, Z., Yue,, X., Li,, W., Niu,, G., Zeng,, W., Wang,, W., Zhou,, K., & Chen,, X. (2014). Dye‐loaded ferritin nanocages for multimodal imaging and Photothermal therapy. Advanced Materials, 26(37), 6401–6408. https://doi.org/10.1002/adma.201400914
Johnson,, E., Cascio,, D., Sawaya,, M. R., Gingery,, M., & Schröder,, I. (2005). Crystalstructures of a tetrahedral open pore ferritin from the hyperthermophilicarchaeon Archaeoglobus fulgidus. Structure, 13(4), 637–648. https://doi.org/10.1016/j.str.2005.01.019
Kabanov,, A. V., & Batrakova,, E. V. (2017). Polymer nanomaterials for drug delivery across the blood brain barrier. In Neuroimmune pharmacology. Cham: Springer International Publishing, 847–868. https://doi.org/10.1007/978-3-319-44022-4
Kang,, H., Rho,, S., Stiles,, W. R., Hu,, S., Baek,, Y., Hwang,, D. W., Kashiwagi,, S., Kim,, M. S., & Choi,, H. S. (2020). Size‐dependent EPR effect of polymeric nanoparticles on tumor targeting. Advanced Healthcare Materials, 9(1), 1901223. https://doi.org/10.1002/adhm.201901223
Kato,, K., Tanaka,, H., Sumizawa,, T., Yoshimura,, M., Yamashita,, E., Iwasaki,, K., & Tsukihara,, T. (2008). A vault ribonucleoprotein particle exhibiting 39‐fold dihedral symmetry. Acta Crystallographica Section D: Biological Crystallography, 64(5), 525–531. https://doi.org/10.1107/S0907444908004277
Kawano,, T., Murata,, M., Kang,, J. H., Piao,, J. S., Narahara,, S., Hyodo,, F., Hamano,, N., Guo,, J., Oguri,, S., Ohuchida,, K., & Hashizume,, M. (2018). Ultrasensitive MRI detection of spontaneous pancreatic tumors with nanocage‐based targeted contrast agent. Biomaterials, 152, 37–46. https://doi.org/10.1016/j.biomaterials.2017.10.029
Kawano,, T., Murata,, M., Piao,, J. S., Narahara,, S., Hamano,, N., Kang,, J. H., & Hashizume,, M. (2015). Systemic delivery of protein nanocages bearing CTT peptides for enhanced imaging of MMP‐2 expression in metastatic tumor models. International Journal of Molecular Sciences, 16(1), 148–158. https://doi.org/10.3390/ijms16010148
Kim,, H. K., Baek,, A. R., Choi,, G., Lee,, J. J., Yang,, J. U., Jung,, H., Lee,, T., Kim,, D., Kim,, M., Cho,, A., Lee,, G. H., & Chang,, Y. (2020). 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. https://doi.org/10.1016/j.biomaterials.2020.119939
Kim,, K., Lee,, M., Park,, H., Kim,, J. H., Kim,, S., Chung,, H., Choi,, K., Kim,, I. S., Seong,, B. L., & Kwon,, I. C. (2006). Cell‐permeable and biocompatible polymeric nanoparticles for apoptosis imaging. Journal of the American Chemical Society, 128(11), 3490–3491. https://doi.org/10.1021/ja057712f
Kim,, K. K., Kim,, R., & Kim,, S. H. (1998). Crystal structure of a small heat‐shock protein. Nature, 394(6693), 595–599. https://doi.org/10.1038/29106
Kitagawa,, T., Kosuge,, H., Uchida,, M., Dua,, M. M., Iida,, Y., Dalman,, R. L., Douglas,, T., & McConnell,, M. V. (2012). RGD‐conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease. Molecular Imaging and Biology, 14(3), 315–324. https://doi.org/10.1007/s11307-011-0495-1
Kumawat,, M. K., Srivastava,, R., Thakur,, M., & Gurung,, R. B. (2017). Graphene quantum dots from Mangifera indica: Application in near‐infrared bioimaging and intracellular nanothermometry. ACS Sustainable Chemistry and Engineering, 5(2), 1382–1391. https://doi.org/10.1021/acssuschemeng.6b01893
Kumawat,, M. K., Thakur,, M., Gurung,, R. B., & Srivastava,, R. (2017). Graphene quantum dots for cell proliferation, nucleus imaging, and photoluminescent sensing applications. Scientific Reports, 7(1), 1–16. https://doi.org/10.1038/s41598-017-16025-w
Lakshmanan,, A., Farhadi,, A., Nety,, S. P., Lee‐Gosselin,, A., Bourdeau,, R. W., Maresca,, D., & Shapiro,, M. G. (2016). Molecular engineering of acoustic protein nanostructures. ACS Nano, 10(8), 7314–7322. https://doi.org/10.1021/acsnano.6b03364
Lakshmanan,, A., Lu,, G. J., Farhadi,, A., Nety,, S. P., Kunth,, M., Lee‐Gosselin,, A., Maresca,, D., Bourdeau,, R. W., Yin,, M., Yan,, J., Witte,, C., Malounda,, D., Foster,, F. S., Schröder,, L., & Shapiro,, M. G. (2017). Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI. Nature Protocols, 12(10), 2050. https://doi.org/10.1038/nprot.2017.081
Li,, C., Li,, F., Zhang,, Y., Zhang,, W., Zhang,, X. E., & Wang,, Q. (2015). Real‐time monitoring surface chemistry‐dependent in vivo behaviors of protein nanocages via encapsulating an NIR‐II Ag2S quantum dot. ACS Nano, 9(12), 12255–12263. https://doi.org/10.1021/acsnano.5b05503
Li,, C., Meng,, Y., Wang,, S., Qian,, M., Wang,, J., Lu,, W., & Huang,, R. (2015). Mesoporous carbon nanospheres featured fluorescent aptasensor for multiple diagnosis of cancer in vitro and in vivo. ACS Nano, 9(12), 12096–12103. https://doi.org/10.1021/acsnano.5b05137
Li,, X., Zhang,, Y., Chen,, H., Sun,, J., & Feng,, F. (2016). Protein nanocages for delivery and release of luminescent ruthenium(II) polypyridyl complexes. ACS Applied Materials and Interfaces, 8(35), 22756–22761. https://doi.org/10.1021/acsami.6b07038
Liang,, M., Tan,, H., Zhou,, J., Wang,, T., Duan,, D., Fan,, K., He,, J., Cheng,, D., Shi,, H., Choi,, H. S., & Yan,, X. (2018). Bioengineered H‐ferritin nanocages for quantitative imaging of vulnerable plaques in atherosclerosis. ACS Nano, 12(9), 9300–9308. https://doi.org/10.1021/acsnano.8b04158
Lim,, Y. T., Noh,, Y. W., Han,, J. H., Cai,, Q. Y., Yoon,, K. H., & Chung,, B. H. (2008). Biocompatible polymer‐nanoparticle‐based bimodal imaging contrast agents for the labeling and tracking of dendritic cells. Small, 4(10), 1640–1645. https://doi.org/10.1002/smll.200800582
Lin,, X., Xie,, J., Niu,, G., Zhang,, F., Gao,, H., Yang,, M., Quan,, Q., Aronova,, M. A., Zhang,, G., Lee,, S., Leapman,, R., & Chen,, X. (2011). Chimeric ferritin nanocages for multiple function loading and multimodal imaging. Nano Letters, 11(2), 814–819. https://doi.org/10.1021/nl104141g
Lu,, G. J., Farhadi,, A., Szablowski,, J. O., Lee‐Gosselin,, A., Barnes,, S. R., Lakshmanan,, A., Bourdeau,, R. W., & Shapiro,, M. G. (2018). Acoustically modulated magnetic resonance imaging of gas‐filled protein nanostructures. Nature Materials, 17(5), 456–463. https://doi.org/10.1038/s41563-018-0023-7
Luo,, P. G., Sahu,, S., Yang,, S.‐T., Sonkar,, S. K., Wang,, J., Wang,, H., LeCroy,, G. E., Cao,, L., & Sun,, Y.‐P. (2013). Carbon “quantum” dots for optical bioimaging. Journal of Materials Chemistry B, 1(16), 2116–2127. https://doi.org/10.1039/c3tb00018d
Luo,, W., Guo,, H., Ye,, Y., Huang,, C., Lin,, L., Li,, L., Wu,, Y., & Chen,, H. (2019). Construction and in vitro studies of magnetic‐apoferritin nanocages conjugated with KGDS peptide targeted at activated platelets for the MRI diagnosis of thrombus. Journal of Nanoparticle Research, 21(8), 1–12. https://doi.org/10.1007/s11051-019-4603-5
Madannejad,, R., Shoaie,, N., Jahanpeyma,, F., Darvishi,, M. H., Azimzadeh,, M., & Javadi,, H. (2019). Toxicity of carbon‐based nanomaterials: Reviewing recent reports in medical and biological systems. Chemico‐Biological Interactions, 307, 206–222. https://doi.org/10.1016/j.cbi.2019.04.036
Malhotra,, N., Lee,, J. S., Liman,, R. A. D., Ruallo,, J. M. S., Villaflore,, O. B., Ger,, T. R., & Der Hsiao,, C. (2020). Potential toxicity of iron oxide magnetic nanoparticles: A review. Molecules, 25(14), 3159. https://doi.org/10.3390/molecules25143159
Maresca,, D., Payen,, T., Lee‐Gosselin,, A., Ling,, B., Malounda,, D., Demené,, C., Tanter,, M., & Shapiro,, M. G. (2020). Acoustic biomolecules enhance hemodynamic functional ultrasound imaging of neural activity. NeuroImage, 209, 116467. https://doi.org/10.1016/j.neuroimage.2019.116467
Michalet,, X., Pinaud,, F.F., Bentolila,, L.A., Tsay,, J.M., Doose,, S.J.J.L., Li,, J.J., Sundaresan,, G., Wu,, A.M., Gambhir,, S.S. & Weiss,, S. (2005). Quantum dots for live cells, in vivo imaging, and diagnostics. Science, 307(5709), 538–545. https://doi.org/10.1126/science.1104274
Molino,, N. M., & Wang,, S.‐W. (2014). Caged protein nanoparticles for drug delivery. Current Opinion in Biotechnology, 28, 75–82. https://doi.org/10.1016/j.copbio.2013.12.007
Mosayebi,, M., Shoemark,, D. K., Fletcher,, J. M., Sessions,, R. B., Linden,, N., Woolfson,, D. N., & Liverpool,, T. B. (2017). Beyond icosahedral symmetry in packings of proteins in spherical shells. Proceedings of the National Academy of Sciences of the United States of America, 114(34), 9014–9019. https://doi.org/10.1073/pnas.1706825114
Nandwana,, V., Ryoo,, S. R., Kanthala,, S., Kumar,, A., Sharma,, A., Castro,, F. C., Li,, Y., Hoffman,, B., Lim,, S., & Dravid,, V. P. (2017). Engineered ferritin nanocages as natural contrast agents in magnetic resonance imaging. RSC Advances, 7(55), 34892–34900. https://doi.org/10.1039/c7ra05681h
Nasrollahi,, F., Sana,, B., Paramelle,, D., Ahadian,, S., Khademhosseini,, A., & Lim,, S. (2020). Incorporation of graphene quantum dots, iron, and doxorubicin in/on ferritin nanocages for bimodal imaging and drug delivery. Advanced Therapeutics, 3(3), 1900183. https://doi.org/10.1002/adtp.201900183
Neu,, U., Woellner,, K., Gauglitz,, G., & Stehle,, T. (2008). Structural basis ofGM1 ganglioside recognition by simian virus 40. Proceedings of the National Academy of Sciences, 105(13), 5219–5224. https://doi.org/10.1073/pnas.0710301105
Ni,, D., Ehlerding,, E. B., & Cai,, W. (2019). Multimodality imaging agents with PET as the fundamental pillar. Angewandte Chemie International Edition, 58(9), 2570–2579. https://doi.org/10.1002/anie.201806853
Nyk,, M., Kumar,, R., Ohulchanskyy,, T. Y., Bergey,, E. J., & Prasad,, P. N. (2008). High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up‐conversion in Tm 3+ and Yb 3+ doped fluoride nanophosphors. Nano Letters, 8(11), 3834–3838. https://doi.org/10.1021/nl802223f
Patel,, T., Zhou,, J., Piepmeier,, J. M., & Saltzman,, W. M. (2012). Polymeric nanoparticles for drug delivery to the central nervous system. Advanced Drug Delivery Reviews, 64(7), 701–705. https://doi.org/10.1016/j.addr.2011.12.006
Perrault,, S. D., Walkey,, C., Jennings,, T., Fischer,, H. C., & Chan,, W. C. W. (2009). Mediating tumor targeting efficiency of nanoparticles through design. Nano Letters, 9(5), 1909–1915. https://doi.org/10.1021/nl900031y
Qiao,, R., Huang,, X., Qin,, Y., Li,, Y., Davis,, T. P., Hagemeyer,, C. E., & Gao,, M. (2020). Recent advances in molecular imaging of atherosclerotic plaques and thrombosis. Nanoscale, 12(15), 8040–8064. https://doi.org/10.1039/d0nr00599a
Ravishankar,, S., & Lim,, S. (2019). Cyclodextrin conjugated ferritin nanocages reduce intracellular cholesterol level in foam cells. Nano Research, 12(12), 2925–2932. https://doi.org/10.1007/s12274-019-2525-2
Resch‐Genger,, U., Grabolle,, M., Cavaliere‐Jaricot,, S., Nitschke,, R., & Nann,, T. (2008). Quantum dots versus organic dyes as fluorescent labels. Nature Methods, 5(9), 763–775. https://doi.org/10.1038/nmeth.1248
Ruan,, S., Chen,, J., Cun,, X., Long,, Y., Tang,, J., Qian,, J., Shen,, S., Jiang,, X., Zhu,, J., He,, Q., & Gao,, H. (2015). Noninvasive in vivo diagnosis of brain glioma using RGD‐decorated fluorescent carbonaceous nanospheres. Journal of Biomedical Nanotechnology, 11(12), 2148–2157. https://doi.org/10.1166/jbn.2015.2105
Sana,, B., Johnson,, E., Le Magueres,, P., Criswell,, A., Cascio,, D., & Lim,, S. (2013). The role of nonconserved residues of Archaeoglobus fulgidusferritin on its unique structure and biophysical properties. Journal of Biological Chemistry, 288(45), 32663–32672. https://doi.org/10.1074/jbc.M113.491191
Sana,, B., Johnson,, E., Sheah,, K., Poh,, C. L., & Lim,, S. (2010). Iron‐based ferritin nanocore as a contrast agent. Biointerphases, 5(3), FA48–FA52. https://doi.org/10.1116/1.3483216
Sana,, B., Poh,, C. L., & Lim,, S. (2012). A manganese–ferritin nanocomposite as an ultrasensitive T2 contrast agent. Chemical Communications, 48(6), 862–864. https://doi.org/10.1039/c1cc15189d
Santra,, S., Yang,, H., Dutta,, D., Stanley,, J. T., Holloway,, P. H., Tan,, W., Moudgil,, B. M., & Mericle,, R. A. (2004). TAT conjugated, FITC doped silica nanoparticles for bioimaging applications. Chemical Communications, 24, 2810–2811. https://doi.org/10.1039/b411916a
Saucier‐Sawyer,, J. K., Deng,, Y., Seo,, Y. E., Cheng,, C. J., Zhang,, J., Quijano,, E., & Saltzman,, W. M. (2015). Systemic delivery of blood‐brain barrier targeted polymeric nanoparticles enhances delivery to brain tissue. Journal of Drug Targeting, 23(7–8), 736–749. https://doi.org/10.3109/1061186X.2015.1065833.Systemic
Sayes,, C. M., Gobin,, A. M., Ausman,, K. D., Mendez,, J., West,, J. L., & Colvin,, V. L. (2005). Nano‐C60 cytotoxicity is due to lipid peroxidation. Biomaterials, 26(36), 7587–7595. https://doi.org/10.1016/j.biomaterials.2005.05.027
Shapiro,, M. G., Goodwill,, P. W., Neogy,, A., Yin,, M., Foster,, F. S., Schaffer,, D. V., & Conolly,, S. M. (2014). Biogenic gas nanostructures as ultrasonic molecular reporters. Nature Nanotechnology, 9(4), 311–316. https://doi.org/10.1038/nnano.2014.32
Sitia,, L., Sevieri,, M., Bonizzi,, A., Allevi,, R., Morasso,, C., Foschi,, D., Corsi,, F., & Mazzucchelli,, S. (2020). Development of tumor‐targeted indocyanine green‐loaded ferritin nanoparticles for intraoperative detection of cancers. ACS Omega, 5(21), 12035–12045. https://doi.org/10.1021/acsomega.0c00244
Srikar,, R., Upendran,, A., & Kannan,, R. (2014). Polymeric nanoparticles for molecular imaging. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 6(3), 245–267. https://doi.org/10.1002/wnan.1259
Sun,, C., Yuan,, Y., Xu,, Z., Ji,, T., Tian,, Y., Wu,, S., Lei,, J., Li,, J., Gao,, N., & Nie,, G. (2015). Fine‐tuned H‐ferritin nanocage with multiple gold clusters as near‐infrared kidney specific targeting nanoprobe. Bioconjugate Chemistry, 26(2), 193–196. https://doi.org/10.1021/bc5005284
Sun,, X., Li,, W., Zhang,, X., Qi,, M., Zhang,, Z., Zhang,, X. E., & Cui,, Z. (2016). In vivo targeting and imaging of atherosclerosis using multifunctional virus‐like particles of simian virus 40. Nano Letters, 16(10), 6164–6171. https://doi.org/10.1021/acs.nanolett.6b02386
Sykes,, E. A., Chen,, J., Zheng,, G., & Chan,, W. C. W. (2014). Investigating the impact of nanoparticle size on active and passive tumor targeting efficiency. ACS Nano, 8(6), 5696–5706. https://doi.org/10.1021/nn500299p
Szabó,, I., Crich,, S. G., Alberti,, D., Kálmán,, F. K., & Aime,, S. (2012). Mn loaded apoferritin as an MRI sensor of melanin formation in melanoma cells. Chemical Communications, 48(18), 2436–2438. https://doi.org/10.1039/c2cc17801j
Terashima,, M., Uchida,, M., Kosuge,, H., Tsao,, P. S., Young,, M. J., Conolly,, S. M., Douglas,, T., & McConnell,, M. V. (2011). Human ferritin cages for imaging vascular macrophages. Biomaterials, 32(5), 1430–1437. https://doi.org/10.1016/j.biomaterials.2010.09.029
Truffi,, M., Fiandra,, L., Sorrentino,, L., Monieri,, M., Corsi,, F., & Mazzucchelli,, S. (2016). Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer. Pharmacological Research, 107, 57–65. https://doi.org/10.1016/j.phrs.2016.03.002
Uchida,, M., Kosuge,, H., Terashima,, M., Willits,, D. A., Liepold,, L. O., Young,, M. J., McConnell,, M. V., & Douglas,, T. (2011). Protein cage nanoparticles bearing the LyP‐1 peptide for enhanced imaging of macrophage‐rich vascular lesions. ACS Nano, 5(4), 2493–2502. https://doi.org/10.1021/nn102863y
Uchida,, M., Maier,, B., Waghwani,, H. K., Selivanovitch,, E., Louise Pay,, S., Avera,, J., Yun,, E., Sandoval,, R. M., Molitoris,, B. A., Zollman,, A., Douglas,, T., & Hato,, T. (2019). The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration. Journal of Clinical Investigation, 129(9), 3941–3951. https://doi.org/10.1172/JCI127511
Wang,, T., He,, J., Duan,, D., Jiang,, B., Wang,, P., Fan,, K., Liang,, M., & Yan,, X. (2019). Bioengineered magnetoferritin nanozymes for pathological identification of high‐risk and ruptured atherosclerotic plaques in humans. Nano Research, 12(4), 863–868. https://doi.org/10.1007/s12274-019-2313-z
Wang,, Z., Huang,, P., Jacobson,, O., Wang,, Z., Liu,, Y., Lin,, L., Lin,, J., Lu,, N., Zhang,, H., Tian,, R., Niu,, G., Liu,, G., & Chen,, X. (2016). Biomineralization‐inspired synthesis of copper sulfide‐ferritin Nanocages as cancer Theranostics. ACS Nano, 10(3), 3453–3460. https://doi.org/10.1021/acsnano.5b07521
Wickline,, S. A., Neubauer,, A. M., Winter,, P., Caruthers,, S., & Lanza,, G. (2006). Applications of nanotechnology to atherosclerosis, thrombosis, and vascular biology. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(3), 435–441. https://doi.org/10.1161/01.ATV.0000201069.47550.8b
Yang,, Y., Qiu,, Z., Hou,, X., & Sun,, L. (2017). Ultrasonic characteristics and cellular properties of Anabaena gas vesicles. Ultrasound in Medicine and Biology, 43(12), 2862–2870. https://doi.org/10.1016/j.ultrasmedbio.2017.08.004
Yao,, H. C., Su,, L., Zeng,, M., Cao,, L., Zhao,, W. W., Chen,, C. Q., Du,, B., & Zhou,, J. (2016). Construction of magnetic‐carbon‐quantum‐dots‐probe‐labeled apoferritin nanocages for bioimaging and targeted therapy. International Journal of Nanomedicine, 11, 4423–4438. https://doi.org/10.2147/IJN.S108039
Yoo,, J.‐W., Chambers,, E., & Mitragotri,, S. (2010). Factors that control the circulation time of nanoparticles in blood: Challenges, solutions and future prospects. Current Pharmaceutical Design, 16(21), 2298–2307. https://doi.org/10.2174/138161210791920496
Yuan,, X., Zhang,, X., Sun,, L., Wei,, Y., & Wei,, X. (2019). Cellular toxicity and immunological effects of carbon‐based Nanomaterials. Particle and Fibre Toxicology, 16(1), 1–27. https://doi.org/10.1186/s12989-019-0299-z
Zhai,, M., Wang,, Y., Zhang,, L., Liang,, M., Fu,, S., Cui,, L., Yang,, M., Gong,, W., Li,, Z., Yu,, L., Xie,, X., Yang,, C., Yang,, Y., & Gao,, C. (2018). Glioma targeting peptide modified apoferritin nanocage. Drug Delivery, 25(1), 1013–1024. https://doi.org/10.1080/10717544.2018.1464082
Zhang,, J., Campbell,, R. E., Ting,, A. Y., & Tsien,, R. Y. (2002). Creating new fluorescent probes for cell biology. Nature Reviews Molecular Cell Biology, 3(12), 906–918. https://doi.org/10.1038/nrm976
Zhang,, J., Zu,, Y., Dhanasekara,, C. S., Li,, J., Wu,, D., Fan,, Z., & Wang,, S. (2017). Detection and treatment of atherosclerosis using nanoparticles. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 9(1), e1412. https://doi.org/10.1002/wnan.1412
Zhang,, Q., Chen,, J., Shen,, J., Chen,, S., Liang,, K., Wang,, H., & Chen,, H. (2019). Inlaying radiosensitizer onto the polypeptide shell of drug‐loaded ferritin for imaging and combinational chemo‐radiotherapy. Theranostics, 9(10), 2779–2790. https://doi.org/10.7150/thno.33472
Zhen,, Z., Tang,, W., Guo,, C., Chen,, H., Lin,, X., Liu,, G., Fei,, B., Chen,, X., Xu,, B., & Xie,, J. (2013). Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer. ACS Nano, 7(8), 6988–6996. https://doi.org/10.1021/nn402199g
Zhen,, Z., Tang,, W., Todd,, T., & Xie,, J. (2014). Ferritins as nanoplatforms for imaging and drug delivery. Expert Opinion on Drug Delivery, 11(12), 1913–1922. https://doi.org/10.1517/17425247.2014.941354
Zheng,, X. T., Ananthanarayanan,, A., Luo,, K. Q., & Chen,, P. (2015). Glowing graphene quantum dots and carbon dots: Properties, syntheses, and biological applications. Small, 11(14), 1620–1636. https://doi.org/10.1002/smll.201402648
Zhou,, Z., & Lu,, Z. R. (2013). Gadolinium‐based contrast agents for magnetic resonance cancer imaging. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 5(1), 1–18. https://doi.org/10.1002/wnan.1198

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