Enhancing radiosensitization in triple-negative breast cancer by aptamer-modified nanoclusters NC-T5-5TR1
Abstract
Radiotherapy is an important part of standard treatment for triple-negative breast cancer (TNBC); however, radioresistance significantly limits therapeutic outcomes. In this study, we developed a novel radiosensitizer based on aptamer-modified silver nanoclusters, NC-T5-5TR1, to potentiate radiotherapy efficacy against TNBC. NC-T5-5TR1 enabled real-time tumor imaging and accurate localization via their intrinsic fluorescence and targeting capability. When combined with ionizing radiation (IR), NC-T5-5TR1 significantly enhanced radiosensitization in vitro, as evidenced by decreased proliferation, increased apoptosis and higher reactive oxygen species (ROS) levels, and also markedly inhibited tumor growth in vivo. Transcriptomic analysis indicated that the IL-6/JAK2/STAT3 signaling pathway was downregulated under NC-T5-5TR1 + IR treatment, which was subsequently validated in vitro and in vivo. Rescue experiments confirmed that IL-6 overexpression reversed NC-T5-5TR1 combined with IR-induced JAK2/STAT3 inhibition and its downstream effects on proliferation, apoptosis, and ROS accumulation. Collectively, our findings demonstrated that NC-T5-5TR1 enhanced the radiosensitivity of TNBC cells, and this effect was associated with the modulation of the IL-6/JAK2/STAT3 axis, offering a promising strategy for improving the therapeutic efficacy of radiotherapy in TNBC.
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Receptor-specific targeting, including HER2-, CXCR4-, and folate-directed systems, was frequently described in the included studies and was associated with increased cellular uptake.
“Receptor-specific targeting, including HER2-, CXCR4-, and folate-directed systems, was frequently described and associated with increased cellular uptake [20,24,29,49,51,55,70].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [70]
Cites
Nanocarriers as an emerging platform for cancer therapy
Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2007.387 · Cited by 8,710 · see citing works
Fisher, B., Anderson, S., Bryant, J., Margolese, R. G., Deutsch, M., Fisher, E. R., Jeong, J.-H., & Wolmark, N. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa022152 · Cited by 6,249 · see citing works
Waks, A. G., & Winer, E. P. (2019) · JAMA · doi:10.1001/jama.2018.19323 · Cited by 4,913 · see citing works
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383 · see citing works
Targeting the IL-6/JAK/STAT3 signalling axis in cancer
Johnson, D. E., O'Keefe, R. A., & Grandis, J. R. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.8 · Cited by 3,110 · see citing works
The ever‐increasing importance of cancer as a leading cause of premature death worldwide
Bray, F., Laversanne, M., Weiderpass, E., & Soerjomataram, I. (2021) · Cancer · doi:10.1002/cncr.33587 · Cited by 2,606 · see citing works
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137 · see citing works
Garrido-Castro, A. C., Lin, N. U., & Polyak, K. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1177 · Cited by 1,451 · see citing works
Nanomaterials for cancer therapy: current progress and perspectives
Cheng, Z., Li, M., Dey, R., & Chen, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01096-0 · Cited by 1,193 · see citing works
DNA-Templated Ag Nanocluster Formation
Petty, J. T., Zheng, J., Hud, N. V., & Dickson, R. M. (2004) · Journal of the American Chemical Society · doi:10.1021/ja031931o · Cited by 1,105 · see citing works
Recent advances in therapeutic strategies for triple-negative breast cancer
Li, Y., Zhang, H., Merkher, Y., Chen, L., Liu, N., Leonov, S. V., & Chen, Y. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01341-0 · Cited by 997 · see citing works
Self-citationOligonucleotide-Stabilized Ag Nanocluster Fluorophores
Richards, C. I., Choi, S., Hsiang, J., Antoku, Y., Vosch, T., Bongiorno, A., Tzeng, Y., & Dickson, R. M. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8005644 · Cited by 862 · see citing works
Fluorescent silver nanoclusters
Díez, I., & Ras, R. H. A. (2011) · Nanoscale · doi:10.1039/c1nr00006c · Cited by 852 · see citing works
Huang, K., Ma, H., Liu, J., Huo, S., Kumar, A., Wei, T., Zhang, X., Jin, S., Gan, Y., Wang, P. C., et al. (2012) · ACS Nano · doi:10.1021/nn301282m · Cited by 843 · see citing works
Cancer active targeting by nanoparticles: a comprehensive review of literature
Bazak, R., Houri, M., Achy, S. E., Kamel, S., & Refaat, T. (2014) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-014-1767-3 · Cited by 766 · see citing works
A DNA−Silver Nanocluster Probe That Fluoresces upon Hybridization
Yeh, H., Sharma, J., Han, J. J., Martinez, J. S., & Werner, J. H. (2010) · Nano Letters · doi:10.1021/nl101773c · Cited by 655 · see citing works
Lee, S. Y., Jeong, E. K., Ju, M. K., Jeon, H. M., Kim, M. Y., Kim, C. H., Park, H. G., Han, S. I., & Kang, H. S. (2017) · Molecular Cancer · doi:10.1186/s12943-016-0577-4 · Cited by 579 · see citing works
Elimination Pathways of Nanoparticles
Poon, W., Zhang, Y.-N., Ouyang, B., Kingston, B. R., Wu, J. L. Y., Wilhelm, S., & Chan, W. C. W. (2019) · ACS Nano · doi:10.1021/acsnano.9b01383 · Cited by 578 · see citing works
Cellular Uptake of Nanoparticles versus Small Molecules: A Matter of Size
Mosquera, J., Garcı́a, I., & Liz‐Marzán, L. M. (2018) · Accounts of Chemical Research · doi:10.1021/acs.accounts.8b00292 · Cited by 489 · see citing works
Application of Radiosensitizers in Cancer Radiotherapy
Gong, L., Zhang, Y., Liu, C., Zhang, M., & Han, S. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s290438 · Cited by 484 · see citing works
Water‐Soluble Fluorescent Silver Nanoclusters
Xu, H., & Suslick, K. S. (2010) · Advanced Materials · doi:10.1002/adma.200904199 · Cited by 476 · see citing works
Strongly emissive individual DNA-encapsulated Ag nanoclusters as single-molecule fluorophores
Vosch, T., Antoku, Y., Hsiang, J., Richards, C. I., González, J. I. R., & Dickson, R. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610677104 · Cited by 460 · see citing works
Functionalization of metal nanoclusters for biomedical applications
Song, X., Goswami, N., Yang, H., & Xie, J. (2016) · The Analyst · doi:10.1039/c6an00773b · Cited by 327 · see citing works
Aptamer-Functionalized Nanoparticles in Targeted Delivery and Cancer Therapy
Fu, Z., & Xiang, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239123 · Cited by 233 · see citing works
Nanomaterials for Cancer Precision Medicine
Wang, Y., Sun, S., Zhang, Z., & Shi, D. (2018) · Advanced Materials · doi:10.1002/adma.201705660 · Cited by 213 · see citing works
Chen, W., Yuan, H., Cao, W., Wang, T., Chen, W., Yu, H., Fu, Y. S., Jiang, B., Zhou, H. Y., Guo, H., et al. (2019) · Theranostics · doi:10.7150/thno.32352 · Cited by 196 · see citing works
One-Pot Synthesis of Aptamer-Functionalized Silver Nanoclusters for Cell-Type-Specific Imaging
Li, J., Zhong, X., Cheng, F.-F., Zhang, J., Jiang, L., & Zhu, J. (2012) · Analytical Chemistry · doi:10.1021/ac3003402 · Cited by 193 · see citing works
Jin, Y. T., Kang, Y., Wang, M., Wu, B., Su, B., Yin, H., Tang, Y., Li, Q., Wei, W., Mei, Q., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00872-9 · Cited by 169 · see citing works
DNA-templated silver nanoclusters: structural correlation and fluorescence modulation
New, S. Y., Lee, S. T., & Su, X. (2016) · Nanoscale · doi:10.1039/c6nr05872h · Cited by 166 · see citing works
Lu, L., Dong, J., Wang, L., Xia, Q., Zhang, D., Kim, H.-J., Yin, T., Fan, S., & Shen, Q. (2018) · Oncogene · doi:10.1038/s41388-018-0340-y · Cited by 166 · see citing works
Fluorescent silver nanoclusters as DNA probes
Obliosca, J. M., Liu, C., & Yeh, H. (2013) · Nanoscale · doi:10.1039/c3nr01601c · Cited by 150 · see citing works
Taghavi, S., Ramezani, M., Alibolandi, M., Abnous, K., & Taghdisi, S. M. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.04.008 · Cited by 145 · see citing works
Beyond the EPR effect: Intravital microscopy analysis of nanoparticle drug delivery to tumors
Belyaev, I. B., Griaznova, O. Y., Yaremenko, A. V., Deyev, S. M., & Zelepukin, I. V. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115550 · Cited by 141 · see citing works
Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis
Chang, R., Song, L., Xu, Y., Wu, Y., Dai, C., Wang, X., Sun, X., Hou, Y., Li, W., Zhan, X., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05852-8 · Cited by 118 · see citing works
CFAssay: statistical analysis of the colony formation assay
Braselmann, H., Michna, A., Heß, J., & Unger, K. (2015) · Radiation Oncology · doi:10.1186/s13014-015-0529-y · Cited by 95 · see citing works
Metallic Nanoclusters for Cancer Imaging and Therapy
Zhang, Q., Yang, M., Zhu, Y., & Mao, C. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170331122757 · Cited by 93 · see citing works
Ai, J., Guo, W., Li, B., Li, T., Li, D., & Wang, E. (2011) · Talanta · doi:10.1016/j.talanta.2011.10.057 · Cited by 77 · see citing works
Self-citationYu, Y., Mok, B., Loh, X. J., & Tan, Y. (2016) · Advanced Healthcare Materials · doi:10.1002/adhm.201600192 · Cited by 75 · see citing works
G-quadruplex enhanced fluorescence of DNA–silver nanoclusters and their application in bioimaging
Zhu, J., Zhang, L., Teng, Y., Lou, B., Jia, X., Gu, X., & Wang, E. (2015) · Nanoscale · doi:10.1039/c5nr03092g · Cited by 67 · see citing works
Ultrasmall Au and Ag Nanoclusters for Biomedical Applications: A Review
Tang, J., Shi, H., Ma, G., Luo, L., & Tang, Z. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.01019 · Cited by 52 · see citing works
Yao, X., Lu, S., Feng, C., Suo, R., Li, H., Zhang, Y., Chen, Q., Lü, J., Wu, B., & Guo, J. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121801 · Cited by 39 · see citing works
Aptamers: Novel Molecules as Diagnostic Markers in Bacterial and Viral Infections?
Zimbres, F. M., Tárnok, A., Ulrich, H., & Wrenger, C. (2013) · BioMed Research International · doi:10.1155/2013/731516 · Cited by 36 · see citing works
Nejabat, M., Eisvand, F., Soltani, F., Alibolandi, M., Taghdisi, S. M., Abnous, K., Hadizadeh, F., & Ramezani, M. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119650 · Cited by 31 · see citing works
Shiridokht, F., Dadashi, H., Vandghanooni, S., Eskandani, M., & Farajollahi, A. (2025) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/j.colsurfb.2024.114220 · Cited by 30 · see citing works
Huang, Y. D., Li, J., Feng, H., Du, H., & Deng, Z. (2025) · Nano Letters · doi:10.1021/acs.nanolett.4c05525 · Cited by 22 · see citing works
Long, L., Xu, J., Qi, X., Pen, Y., Wang, C., Jiang, W., Peng, X., Hu, Z., Yi, W., Xie, L., et al. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116500 · Cited by 10 · see citing works
Klębowski, B., Gałuszka-Bulaga, A., Strawski, M., Kęsik, J. J., Baran, J., & Depciuch, J. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.115192 · Cited by 3 · see citing works
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Lunca, S., Morarasu, S., & Dimofte, G. M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146522 · Cited by 2 · see citing works
“Receptor-specific targeting, including HER2, CXCR4, and folate-directed systems, was frequently described and associated with increased cellular uptake [20,24,29,49,51,55,70].”
Nanoparticle‐Based Radiosensitizers in Cancer Therapy: Current Advances and Clinical Prospects
Sandu, R., Doddi, T., Maddila, J. R., & Rengan, A. K. (2026) · Advanced Therapeutics · doi:10.1002/adtp.70171
Azhar, M. A., Ahmed, S., Altuhami, A., Shabab, M., Assiri, A. M., Broering, D. C., & Mir, T. A. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1987479
- Authors
- Kan, X., Wang, J., Li, Y., Li, D., Li, F., Huang, C., & Liu, P.
- Affiliations
- Southeast University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Liu, Peidang
- ORCID
- Liu, Peidang
- Venue
- Colloids and Surfaces B: Biointerfaces
- Publisher
- Elsevier BV
- Published
- 2026-04
- Volume
- 260
- Pages
- 115397
- ISSN
- 0927-7765 (ISSN-L)
- OpenAlex
- W7117108211
- Cited by
- 3
- References
- 47
- Citations by year
- 2026: 3
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Colloids and Surfaces B Biointerfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81771980, 81571805)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Nanocluster Synthesis and Applications
- Keywords
- triple-negative breast cancer, radiosensitization, silver nanoclusters, radioresistance (biology), IL-6/JAK2/STAT3 signaling, reactive oxygen species, apoptosis, tumor imaging, ionizing radiation, combination therapy
- MeSH terms
- Animals, Female, Humans, Mice, Inbred BALB C, Mice, Nude, Radiation-Sensitizing Agents, Radiation, Ionizing, Silver, Signal Transduction, Interleukin-6, Apoptosis, Reactive Oxygen Species, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice, Aptamers, Nucleotide, Janus Kinase 2, Metal Nanoparticles, Triple Negative Breast Neoplasms
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