Radionuclide-embedded gold nanoparticles for enhanced dendritic cell-based cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence
Source abstract
Abstract
Radionuclide-embedded gold nanoparticles (RIe-AuNPs) were developed as a highly sensitive and stable nuclear and optical imaging agent for efficient dendritic cell (DC)-based immunotherapy and sensitive tracking of DC-migration to lymph nodes. The RIe-AuNPs were synthesized via simple and straightforward DNA-based radiolabeling chemistry and additional Au shell formation strategies, leading to high radiosensitivity and excellent in vivo stability. The RIe-AuNPs exert no adverse effects on the biological functions of DCs, and labeled DCs show strong antitumor immunity for lung cancer. Furthermore, the high radiosensitivity of the RIe-AuNPs allows for sensitive and long-term monitoring of DC migration to draining lymph nodes. The developed Cerenkov radiation-based optical imaging approach provides quantitative and sensitive results comparable with that of positron emission tomography imaging. These results highlight the strong potential of the RIe-AuNPs as a highly sensitive and stable nuclear and optical imaging platform for future bioimaging application such as cell tracking and tumor imaging. Gold-based imaging agents containing safely implanted radioisotopes can make it simpler to track dendritic cells in vivo. Dendritic cells (DCs) are a key part of the human immune system, where they patrol and signal against foreign invaders. Efforts to track DCs in vivo are often hampered by imaging agents that are unstable or give poor signals in the body. The research team from South Korea found that modifying gold nanoparticle with adenine-rich DNA strands enabled loading of large quantities of iodine radioisotopes. After coating the nanoparticles with a protective gold shell, the team used them to label DCs injected into live mice. The positron emission tomography (PET) permitted sensitive tracking of DCs in the draining lymph node, also an optical imaging modality based on Cerenkov luminescence showed sensitive imaging capability comparable with that of PET. Herein, we provide a simple and straightforward DNA-based radiolabeling chemistry and additional Au shell formation strategy to obtain radionuclide-embedded gold nanoparticles (RIe-AuNPs) with a high radiosensitivity and excellent in vivo stability. The migration of DCs labeled with RIe-AuNPs to draining lymph nodes was monitored very sensitively and for a long time. The biological function of DCs labeled with RIe-AuNP was not altered and it showed strong antitumor immunity. Because of densely conjugated radioisotopes in RIe-AuNPs, we could obtain strong Cerenkov optical signal comparable with that of positron emission tomography.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Immunotherapy and Immune Responses · Nanoplatforms for cancer theranostics · Cancer Immunotherapy and Biomarkers
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (40)
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1. Boisselier, E. & Astruc, D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev. 38, 1759–1782 (2009).10.1039/b806051g ↗
2. Ghosh, P., Han, G., De, M., Kim, C. K. & Rotello, V. M. Gold nanoparticles in delivery applications. Adv. Drug Deliver. Rev. 60, 1307–1315 (2008).10.1016/j.addr.2008.03.016 ↗
3. Bardhan, R., Lal, S., Joshi, A. & Halas, N. J. Theranostic nanoshells: from probe design to imaging and treatment of cancer. Acc. Chem. Res. 44, 936–946 (2011).10.1021/ar200023x ↗
4. Lim, D. K., Jeon, K.-S., Hwang, J.-H., Kim, H., Kwon, S., Suh, Y. D. & Nam, J. M. Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap. Nat. Nanotechnol. 6, 452–460 (2011).10.1038/nnano.2011.79 ↗
5. Morales-Avila, E., Ferro-Flores, G., Ocampo-García, B. E., De León-Rodríguez, L. M., Santos-Cuevas, C. L., García-Becerra, R., Medina, L. A. & Gómez-Oliván, L. Multimeric system of 99mTc-labeled gold nanoparticles conjugated to c[RGDfK(C)] for molecular imaging of tumor alpha(v)beta(3) expression. Bioconjugate Chem. 22, 913–922 (2011).10.1021/bc100551s ↗
6. Zhao, Y., Sultan, D., Detering, L., Cho, S., Sun, G., Pierce, R., Wooley, K. L. & Liu, Y. Copper-64-alloyed gold nanoparticles for cancer imaging: improved radiolabel stability and diagnostic accuracy. Angew. Chem. 53, 156–159 (2014).10.1002/anie.201308494 ↗
7. Sun, X., Huang, X., Yan, X., Wang, Y., Guo, J. & Jacobson, O. Chelator-free (64)Cu-integrated gold nanomaterials for positron emission tomography imaging guided photothermal cancer therapy. ACS Nano 8, 8438–8446 (2014).10.1021/nn502950t ↗
8. Harris, J. M. & Chess, R. B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2, 214–221 (2003).10.1038/nrd1033 ↗
9. Palucka, K. & Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer 12, 265–277 (2012).10.1038/nrc3258 ↗
10. Ardavin, C., Amigorena, S. & Reis E Sousa, C. Dendritic cells: immunobiology and cancer immunotherapy. Immunity 20, 17–23 (2004).10.1016/S1074-7613(03)00352-2 ↗
11. Randolph, G. J., Angeli, V. & Swartz, M. A. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat. Rev. Immunol. 5, 617–628 (2005).10.1038/nri1670 ↗
12. de Vries, I. J., Lesterhuis, W. J., Barentsz, J. O., Verdijk, P., van Krieken, J. H., Boerman, O. C., Oyen, W. J., Bonenkamp, J. J., Boezeman, J. B., Adema, G. J., Bulte, J. W., Scheenen, T. W., Punt, C. J., Heerschap, A. & Figdor, C. G. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat. Biotechnol. 23, 1407–1413 (2005).10.1038/nbt1154 ↗
13. Ahrens, E. T., Flores, R., Xu, H. & Morel, P. A. In vivo imaging platform for tracking immunotherapeutic cells. Nat. Biotechnol. 23, 983–987 (2005).10.1038/nbt1121 ↗
14. Wu, C., Xu, Y., Yang, L., Wu, J., Zhu, W., Li, D., Cheng, Z., Xia, C., Guo, Y. & Gong, Q. Negatively charged magnetite nanoparticle clusters as efficient MRI probes for dendritic cell labeling and in vivo tracking. Adv. Funct. Mater. 25, 3581–3591 (2015).10.1002/adfm.201501031 ↗
15. Xiang, J., Xu, L., Gong, H., Zhu, W., Wang, C., Xu, J., Feng, L., Cheng, L., Peng, R. & Liu, Z. Antigen-loaded upconversion nanoparticles for dendritic cell stimulation, tracking, and vaccination in dendritic cell-based immunotherapy. ACS Nano 9, 6401–6411 (2015).10.1021/acsnano.5b02014 ↗
16. Culver, J., Akers, W. & Achilefu, S. Multimodality molecular imaging with combined optical and SPECT/PET modalities. J. Nucl. Med. 49, 169–172 (2008).10.2967/jnumed.107.043331 ↗
17. Adonai, N., Nguyen, K. N., Walsh, J., Iyer, M., Toyokuni, T., Phelps, M. E., McCarthy, T., McCarthy, D. W. & Gambhir, S. S. Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc. Natl Acad. Sci. USA 99, 3030–3035 (2002).10.1073/pnas.052709599 ↗
18. Thorek, D. L. J., Robertson, R., Bacchus, W. A., Hahn, J., Rothberg, J., Beattie, B. J. & Grimm, J. Cerenkov imaging—A new modality for molecular imaging. Am. J. Nucl. Med. Mol. Imaging 2, 163 (2012).
19. Robertson, R., Germanos, M. S., Li, C., Mitchell, G. S., Cherry, S. R. & Silva, M. D. Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys. Med. Biol. 54, N355–N365 (2009).10.1088/0031-9155/54/16/N01 ↗
20. Xu, Y., Liu, H. & Cheng, Z. Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging. J. Nucl. Med. 52, 2009–2018 (2011).10.2967/jnumed.111.092965 ↗
21. Lutz, M. B., Kukutsch, N., Ogilvie, A. L., Rössner, S., Koch, F., Romani, N. & Schuler, G. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods 223, 77–92 (1999).10.1016/S0022-1759(98)00204-X ↗
22. Hurst, S. J., Lytton-Jean, A. K. & Mirkin, C. A. Maximizing DNA loading on a range of gold nanoparticle sizes. Anal. Chem. 78, 8313–8318 (2006).10.1021/ac0613582 ↗
23. Rosi, N. L., Giljohann, D. A., Thaxton, C. S., Lytton-Jean, A. K. R., Han, M. S. & Mirkin, C. A. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312, 1027–1030 (2006).10.1126/science.1125559 ↗
24. Mirkin, C. A., Letsinger, R. L., Mucic, R. C. & Storhoff, J. J. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382, 607–609 (1996).10.1038/382607a0 ↗
25. Kim, Y.-H., Jeon, J., Hong, S. H., Rhim, W.-K., Lee, Y.-S., Youn, H., Chung, J. K., Lee, M. C., Lee, D. S., Kang, K. W. & Nam, J. M. Tumor targeting and imaging using cyclic RGD-PEGylated gold nanoparticle probes with directly conjugated iodine-125. Small 7, 2052–2060 (2011).10.1002/smll.201100927 ↗
26. Steinman, R. M. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296 (1991).10.1146/annurev.iy.09.040191.001415 ↗
27. Zhong, H., Han, B., Tourkova, I. L., Lokshin, A., Rosenbloom, A., Shurin, M. R. & Shurin, G. V. Low-dose paclitaxel prior to intratumoral dendritic cell vaccine modulates intratumoral cytokine network and lung cancer growth. Clin. Cancer Res. 13, 5455–5462 (2007).10.1158/1078-0432.CCR-07-0517 ↗
28. Tian, X., Zhu, M., Tian, Y., Ramm, G. A., Zhao, Y. & Nie, G. A membrane vesicle-based dual vaccine against melanoma and Lewis lung carcinoma. Biomaterials 33, 6147–6154 (2012).10.1016/j.biomaterials.2012.05.034 ↗
29. Som, P., Atkins, H. L., Bandoypadhyay, D., Fowler, J. S., MacGregor, R. R., Matsui, K., Oster, Z. H., Sacker, D. F., Shiue, C. Y., Turner, H., Wan, C. N., Wolf, A. P. & Zabinski, S. V. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection. J. Nucl. Med. 21, 670–675 (1980).
30. Kelloff, G. J., Hoffman, J. M., Johnson, B., Scher, H. I., Siegel, B. A., Cheng, E. Y., Cheson, B. D., O'shaughnessy, J., Guyton, K. Z., Mankoff, D. A., Shankar, L., Larson, S. M., Sigman, C. C., Schilsky, R. L. & Sullivan, D. C. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin. Cancer Res. 11, 2785–2808 (2005).10.1158/1078-0432.CCR-04-2626 ↗
31. Solanki, A., Cheung, S.-T. D., Yin, P. T., Kapera, R., Chhowalla, M. & Li, K-B. Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures. Adv. Mater. 25, 5477–5482 (2013).10.1002/adma.201302219 ↗
32. Han, J., Kim, B., Shin, J.-Y., Ryu, S., Noh, M., Woo, J., Park, J. S., Lee, Y., Lee, N., Hyeon, T., Choi, D. & Kim, B. S. Iron oxide nanoparticle-mediated development of cellular gap junction crosstalk to improve mesenchymal stem cells' therapeutic efficacy for myocardial infarction. ACS Nano 9, 2805–2819 (2015).10.1021/nn506732n ↗
33. Park, J., Kim, B., Han, J., Oh, J., Park, S., Ryu, S., Jung, S., Shin, J. Y., Lee, B. S., Hong, B. H., Choi, D. & Kim, B. S. Graphene oxide flakes as a cellular adhesive: Prevention of reactive oxygen species mediated death of implanted cells for cardiac repair. ACS Nano 9, 4987–4999 (2015).10.1021/nn507149w ↗
34. Noh, Y. W., Lim, Y. T. & Chung, B. H. Noninvasive imaging of dendritic cell migration into lymph nodes using near-infrared fluorescent semiconductor nanocrystals. Faseb J. 22, 3908–3918 (2008).10.1096/fj.08-112896 ↗
35. Baumjohann, D., Hess, A., Budinsky, L., Brune, K., Schuler, G. & Lutz, M. B. In vivo magnetic resonance imaging of dendritic cell migration into the draining lymph nodes of mice. Eur. J. Immunol. 36, 2544–2555 (2006).10.1002/eji.200535742 ↗
36. Martelli, C., Borelli, M., Ottobrini, L., Rainone, V., Degrassi, A., Russo, M., Gianelli, U., Bosari, S., Fiorini, C., Trabattoni, D., Clerici, M. & Lucignani, G. In vivo imaging of lymph node migration of MNP- and (111)In-labeled dendritic cells in a transgenic mouse model of breast cancer (MMTV-Ras). Mol. Imaging Biol. 14, 183–196 (2012).10.1007/s11307-011-0496-0 ↗
37. Martín-Fontecha, A., Sebastiani, S., Höpken, U. E., Uguccioni, M., Lipp, M., Lanzavecchia, A. & Sallusto, F. Regulation of dendritic cell migration to the draining lymph node: Impact on T lymphocyte traffic and priming. J. Exp. Med. 198, 615–621 (2003).10.1084/jem.20030448 ↗
38. Cho, N. H., Cheong, T. C., Min, J. H., Wu, J. H., Lee, S. J., Kim, D., Yang, J. S., Kim, S., Kim, Y. K. & Seong, S. Y. A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy. Nat. Nanotechnol. 6, 675–682 (2011).10.1038/nnano.2011.149 ↗
39. Creusot, R. J., Yaghoubi, S. S., Chang, P., Chia, J., Contag, C. H., Gambhir, S. S. & Fathman, C. G. Lymphoid-tissue-specific homing of bone-marrow-derived dendritic cells. Blood 113, 6638–6647 (2009).10.1182/blood-2009-02-204321 ↗
40. Kupiec-Weglinski, J. W., Austyn, J. M. & Morris, P. J. Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues. J. Exp. Med. 167, 632–645 (1988).10.1084/jem.167.2.632 ↗