Metformin-loaded chitosan nanoparticles augment silver nanoparticle-induced radiosensitization in breast cancer cells during radiation therapy
Abstract
Recent research has focused on enhancing tumor response to radiation therapy using radiosensitizers to increase radiation absorption by cancerous tissues. This study utilized silver nanoparticles (AgNPs) as radiation sensitizers and chitosan as a nanocarrier to deliver metformin to breast cancer cells. Metformin-loaded chitosan nanoparticles (Met NPs) and AgNPs were synthesized and characterized. MCF-7 breast cancer cells were pretreated with Met NPs, followed by treatment with AgNPs and irradiation with X-rays at 2, 4, and 8 Gy doses. Cellular cytotoxicity, apoptosis, DNA damage, and 3D spheroid formation were evaluated. The synthesized Met NPs and AgNPs had average diameters of 51.5 ± 9.4 nm and 3.02 ± 0.03 nm, respectively. Cellular cytotoxicity assessment revealed the highest cytotoxicity in MCF-7 cells pretreated with Met NPs, treated with AgNPs, and irradiated with 8 Gy. Flow cytometry analysis demonstrated a 67.58 % apoptosis rate in cells pretreated with Met NPs, compared to 30.42 % in cells pretreated with plain metformin. DAPI staining revealed a 1.8-fold increase in DNA damage in cells pretreated with Met NPs and Ag NPs upon exposure to radiation. The 3D spheroid culture model confirmed a 60 % enhancement in the radiosensitivity of breast cancer cells in the presence of Met NPs and Ag NPs. The combination of Met NPs and Ag NPs represents a promising strategy to improve the therapeutic efficacy of radiation therapy for breast cancer treatment. The delivery of metformin can potentiate the radiosensitizing effects of Ag NPs, offering a novel approach to enhance cancer cells' response to radiation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Additional findings included decreased cell viability and increased apoptosis following combined nanoparticle and radiotherapy treatment.
“Additional findings included decreased cell viability and increased apoptosis following combined nanoparticle and radiotherapy treatment [20,27,33,50,59,72].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [59]
Cites
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21492 · Cited by 84,109 · see citing works
Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
Trachootham, D., Alexandre, J., & Huang, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2803 · Cited by 5,452 · see citing works
Metformin: historical overview
Bailey, C. J. (2017) · Diabetologia · doi:10.1007/s00125-017-4318-z · Cited by 1,079 · see citing works
Chitosan as an environment friendly biomaterial – a review on recent modifications and applications
Bakshi, P. S., Selvakumar, D., Kadirvelu, K., & Kumar, N. S. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.10.113 · Cited by 1,020 · see citing works
Using Nanoparticles to Enable Simultaneous Radiation and Photodynamic Therapies for Cancer Treatment
Chen, W., & Zhang, J. (2006) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2006.327 · Cited by 560 · see citing works
Metformin and Its Benefits for Various Diseases
Lv, Z., & Guo, Y. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00191 · Cited by 544 · see citing works
Sarkar, S., Guibal, E., Quignard, F., & SenGupta, A. K. (2012) · Journal of Nanoparticle Research · doi:10.1007/s11051-011-0715-2 · Cited by 489 · see citing works
Zhang, Q., Li, W., Moran, C. H., Zeng, J., Chen, J., Wen, L., & Younan Xia, A. (2010) · Journal of the American Chemical Society · doi:10.1021/ja104931h · Cited by 441 · see citing works
Avadi, M. R., Sadeghi, A. M. M., Dounighi, N. M., Abedin, S., Atyabi, F., Dinarvand, R., & Rafiee‐Tehrani, M. (2009) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2009.04.007 · Cited by 406 · see citing works
The blooming of the French lilac
Witters, L. A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14178 · Cited by 370 · see citing works
Effect of chitosan and chitosan-nanoparticles on post harvest quality of banana fruits
Lustriane, C., Dwivany, F. M., Suendo, V., et al. (2018) · Journal of Plant Biotechnology · doi:10.5010/jpb.2018.45.1.036 · Cited by 339 · see citing works
Guo, D., Zhu, L., Huang, Z., Zhou, H., Ge, Y., Ma, W., Wu, J., Zhang, X., Zhou, X., Zhang, Y. L., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.07.015 · Cited by 309 · see citing works
Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways
Chairuangkitti, P., Lawanprasert, S., Roytrakul, S., Aueviriyavit, S., Phummiratch, D., Kulthong, K., Pithi Chanvorachote, B., & Maniratanachote, R. (2012) · Toxicology in Vitro · doi:10.1016/j.tiv.2012.08.021 · Cited by 292 · see citing works
Repurposing metformin: an old drug with new tricks in its binding pockets
Pryor, R., & Cabreiro, F. (2015) · Biochemical Journal · doi:10.1042/bj20150497 · Cited by 280 · see citing works
Size Distribution of Silver Nanoparticles: UV-Visible Spectroscopic Assessment
Desai, R., Mankad, V. H., Gupta, S. K., et al. (2012) · Nanoscience and Nanotechnology Letters · doi:10.1166/nnl.2012.1278 · Cited by 270 · see citing works
Wu, X., Redmond, P. L., Liu, H., Chen, Y., Steigerwald, M. L., & Brus, L. E. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8018669 · Cited by 262 · see citing works
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
Testa, U., Castelli, G., & Pelosi, E. (2020) · Medical Sciences · doi:10.3390/medsci8010018 · Cited by 226 · see citing works
Metformin – its potential anti-cancer and anti-aging effects
Podhorecka, M., Ibanez, B., & Dmoszyńska, A. (2017) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.5604/01.3001.0010.3801 · Cited by 205 · see citing works
Miethling-Graff, R., Rumpker, R., Richter, M., et al. (2014) · Toxicology in Vitro · doi:10.1016/j.tiv.2014.06.005 · Cited by 182 · see citing works
One-dimensional silver nanowires synthesized by self-seeding polyol process
Mao, H., Feng, J., Ma, X., et al. (2012) · Journal of Nanoparticle Research · doi:10.1007/s11051-012-0887-4 · Cited by 168 · see citing works
Hejjaji, E. M. A., Smith, A. M., & Morris, G. A. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.09.185 · Cited by 151 · see citing works
Marini, C., Salani, B., Massollo, M., Amaro, A. A., Esposito, A. I., Orengo, A. M., Capitanio, S., Emionite, L., Riondato, M., Bottoni, G., et al. (2013) · Cell Cycle · doi:10.4161/cc.26461 · Cited by 144 · see citing works
Govender, R., Phulukdaree, A., Gengan, R. M., Anand, K., & Chuturgoon, A. A. (2013) · Journal of Nanobiotechnology · doi:10.1186/1477-3155-11-5 · Cited by 130 · see citing works
Genotoxicity effects of silver nanoparticles on wheat (Triticum aestivum L.) root tip cells
Abdelsalam, N. R., Abdel‐Megeed, A., Ali, H. M., et al. (2018) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2018.02.069 · Cited by 128 · see citing works
Salani, B., Marini, C., Río, A. D., Ravera, S., Massollo, M., Orengo, A. M., Amaro, A. A., Passalacqua, M., Maffioli, S., Pfeffer, U., et al. (2013) · Scientific Reports · doi:10.1038/srep02070 · Cited by 120 · see citing works
Stellate Plasmonic Exosomes for Penetrative Targeting Tumor NIR-II Thermo-Radiotherapy
Zhu, D., Lyu, M., Huang, Q., Suo, M., Liu, Y., Jiang, W., Duo, Y., & Fan, K. (2020) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.0c09969 · Cited by 117 · see citing works
Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review
Ganesan, R., Jang, Y., Suh, J., Kim, H.-S., Ahn, S. H., & Kim, T. (2020) · Cancers · doi:10.3390/cancers12030664 · Cited by 105 · see citing works
Zhu, D., Liu, Z., Li, Y., Huang, Q., Xia, L., & Li, K. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120894 · Cited by 105 · see citing works
Metformin: A Novel but Controversial Drug in Cancer Prevention and Treatment
Sui, X., Xu, Y., Wang, X., Han, W., Pan, H., & Xiao, M. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00577 · Cited by 91 · see citing works
Laot, C. M., Marand, E., & Oyama, H. T. (1999) · Polymer · doi:10.1016/s0032-3861(98)80003-7 · Cited by 85 · see citing works
Wu, H., Wu, I.-D., & Chang, F. (2001) · Polymer · doi:10.1016/s0032-3861(00)00213-5 · Cited by 84 · see citing works
Synthesis of silver nanoparticle using D. carota extract
Umadevi, M., Shalini, S., & Bindhu, M. R. (2012) · Advances in Natural Sciences Nanoscience and Nanotechnology · doi:10.1088/2043-6262/3/2/025008 · Cited by 84 · see citing works
Ning, S., Zhang, T., Lyu, M., Lam, J. W. Y., Zhu, D., Huang, Q., & Tang, B. Z. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122034 · Cited by 79 · see citing works
Mucoadhesive and mucopenetrating chitosan nanoparticles for glycopeptide antibiotic administration
Abruzzo, A., Giordani, B., Miti, A., Vitali, B., Zuccheri, G., Cerchiara, T., Luppi, B., & Bigucci, F. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120874 · Cited by 76 · see citing works
Li, J., Ying, S., Ren, H., Dai, J., Zhang, L., Liang, L., Wang, Q., Shen, Q., & Shen, J. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119241 · Cited by 73 · see citing works
Vu, X. H., Dien, N. D., Phạm, T. T. H., et al. (2020) · RSC Advances · doi:10.1039/d0ra07869g · Cited by 69 · see citing works
Nokhodi, F., Nekoei, M., & Goodarzi, M. T. (2022) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-022-06647-6 · Cited by 63 · see citing works
Derakhshankhah, H., Haghshenas, B., Eskandani, M., et al. (2022) · Materials Today Communications · doi:10.1016/j.mtcomm.2022.103148 · Cited by 59 · see citing works
Self-citationEskandani, M., & Nazemiyeh, H. (2014) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2014.04.009 · Cited by 57 · see citing works
Self-citationPhysico-chemical/biological properties of tripolyphosphate cross-linked chitosan based nanofibers
Sarkar, S. D., Farrugia, B. L., Dargaville, T. R., & Dhara, S. (2012) · Materials Science and Engineering C · doi:10.1016/j.msec.2012.12.066 · Cited by 55 · see citing works
Zamanlu, M., Eskandani, M., Barar, J., Jaymand, M., Pakchin, P. S., & Farhoudi, M. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.101165 · Cited by 54 · see citing works
Self-citationYamamoto, S., Fujiwara, K., & Watarai, H. (2004) · Analytical Sciences · doi:10.2116/analsci.20.1347 · Cited by 48 · see citing works
Hosseini, S. S., Jebelli, A., Vandghanooni, S., et al. (2022) · Chemical Engineering Journal · doi:10.1016/j.cej.2022.135988 · Cited by 47 · see citing works
Self-citationLiang, B., Xie, Y., Fang, Z., et al. (2014) · Journal of Nanoparticle Research · doi:10.1007/s11051-014-2485-0 · Cited by 46 · see citing works
Combination Glucose-Lowering Therapy Plans in T2DM: Case-Based Considerations
Blonde, L., Dipp, S., & Cadena, D. (2018) · Advances in Therapy · doi:10.1007/s12325-018-0694-0 · Cited by 45 · see citing works
Jafarizad, A., Taghizadehgh-Alehjougi, A., Eskandani, M., Hatamzadeh, M., Abbasian, M., Mohammad‐Rezaei, R., Mohammadzadeh, M., Toğar, B., & Jaymand, M. (2018) · Bio-Medical Materials and Engineering · doi:10.3233/bme-171721 · Cited by 41 · see citing works
Self-citationDing, R., Xie, F., Hu, Y., et al. (2017) · Drug Delivery · doi:10.1080/10717544.2016.1247927 · Cited by 38 · see citing works
Preparation of Spherical and Triangular Silver Nanoparticles by a Convenient Method
Li, K., Jia, X., Tang, A., et al. (2012) · Integrated ferroelectrics · doi:10.1080/10584587.2012.686405 · Cited by 36 · see citing works
Mohanty, J. R., Das, S. N., Das, H. C., et al. (2014) · Fibers and Polymers · doi:10.1007/s12221-014-1062-6 · Cited by 35 · see citing works
Solid dispersions of dihydroartemisinin in polyvinylpyrrolidone
Ansari, M. T., & Sunderland, V. B. (2008) · Archives of Pharmacal Research · doi:10.1007/s12272-001-1169-6 · Cited by 34 · see citing works
Treatment Strategies and Survival Outcomes in Breast Cancer
Cheung, K. (2020) · Cancers · doi:10.3390/cancers12030735 · Cited by 33 · see citing works
Ning, S., Suo, M., Huang, Q., Gao, S., Qiao, K., Lyu, M., Huang, Q., Zhang, T., & Tang, B. Z. (2023) · Nano Today · doi:10.1016/j.nantod.2023.102106 · Cited by 32 · see citing works
Eskandani, M., Eskandani, M., Vandghanooni, S., et al. (2022) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2022.112365 · Cited by 30 · see citing works
Self-citationVandghanooni, S., Rasoulian, F., Eskandani, M., Nakhjavani, S. A., & Eskandani, M. (2021) · Pharmaceutical Development and Technology · doi:10.1080/10837450.2021.1963276 · Cited by 28 · see citing works
Self-citationPreparation and visible-light photochromism of phosphomolybdic acid/polyvinylpyrrolidone hybrid film
Sun, Y. J., Wang, X., Lu, Y.-M., et al. (2014) · Chemical Research in Chinese Universities · doi:10.1007/s40242-014-4160-5 · Cited by 27 · see citing works
Unexploited Antineoplastic Effects of Commercially Available Anti-Diabetic Drugs
Papanagnou, P., Stivarou, T., & Tsironi, M. (2016) · Pharmaceuticals · doi:10.3390/ph9020024 · Cited by 25 · see citing works
Xia, H., Tang, C., Gui, H., et al. (2012) · Bioscience Reports · doi:10.1042/bsr20120065 · Cited by 24 · see citing works
Upadhyay, M., Vardhan, H., & Mishra, B. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.101480 · Cited by 24 · see citing works
Rouhi, A. A., Valizadeh, A., Sedghizadeh, N., Pozharani, L. B., Dadashi, H., Kazempour, M., Adibkia, K., Vandghanooni, S., & Eskandani, M. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.105734 · Cited by 20 · see citing works
Self-citationApplication of Radiosensitizers in Cancer Radiotherapy [Corrigendum]
Gong, L., Zhang, Y., Liu, C., et al. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s352169 · Cited by 14 · see citing works
Eskandani, M., Mohabbat, A., Karimiyan, A., Dadashi, H., Adibkia, K., Sanaat, Z., & Vandghanooni, S. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.105278 · Cited by 11 · see citing works
Self-citationChuchita, C. (2018) · Indonesian Journal of Biotechnology (Universitas Gadjah Mada) · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Shiridokht, F., Kehtari, P., Eskandani, M., Farajollahi, A., & Vandghanooni, S. (2025) · International Journal of Pharmaceutics: X · doi:10.1016/j.ijpx.2025.100419 · Cited by 4 · see citing works
Self-citationKan, X., Wang, J., Li, Y., Li, D., Li, F., Huang, C., & Liu, P. (2026) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/j.colsurfb.2025.115397 · Cited by 3 · see citing works
Lunca, S., Morarasu, S., & Dimofte, G. M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146522 · Cited by 2 · see citing works
“Additional findings included decreased cell viability and increased apoptosis following combined nanoparticle and radiotherapy treatment [20,27,33,50,59,72].”
- Authors
- Shiridokht, F., Dadashi, H., Vandghanooni, S., Eskandani, M., & Farajollahi, A.
- Affiliations
- Tabriz University of Medical Sciences (IR)
- Corresponding author
- Eskandani, Morteza
- Farajollahi, Alireza
- Venue
- Colloids and Surfaces B: Biointerfaces
- Publisher
- Elsevier BV
- Published
- 2025-01
- Volume
- 245
- Pages
- 114220
- ISSN
- 0927-7765 (ISSN-L)
- OpenAlex
- W4402340243
- Cited by
- 30
- References
- 62
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 4
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Colloids and Surfaces B Biointerfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tabriz University of Medical Sciences
- Tabriz University of Medical Sciences Research Center for Pharmaceutical Nanotechnology (72189)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Physical Sciences › Materials Science › Polymers and Plastics › Polymer Nanocomposite Synthesis and Irradiation
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Keywords
- metformin, chitosan nanoparticles, silver nanoparticles, radiosensitization, breast cancer, radiotherapy, MCF-7 cells, apoptosis, DNA damage, 3D spheroid culture, drug delivery, combination therapy
- MeSH terms
- Breast Neoplasms, Cell Survival, DNA Damage, Female, Humans, Metformin, Particle Size, Radiation-Sensitizing Agents, Silver, Apoptosis, Chitosan, Nanoparticles, Metal Nanoparticles, MCF-7 Cells
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
