<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Current Nanomaterials</journal-id><journal-title-group><journal-title xml:lang="en">Current Nanomaterials</journal-title><trans-title-group xml:lang="ru"><trans-title>Current Nanomaterials</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2405-4615</issn><issn publication-format="electronic">2405-4623</issn><publisher><publisher-name xml:lang="en">Bentham Science</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">646254</article-id><article-id pub-id-type="doi">10.2174/2405461508666230816090519</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>Materials Science and Nanotechnology</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Quantitative Characterization of the Effect of Biogenic silver-based Nanoparticles on Breast Cancer Cells by High Content Analysis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ferreira</surname><given-names>Veronica</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Eugenio</surname><given-names>Mateus</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Del Nery</surname><given-names>Elaine</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>de Souza</surname><given-names>Wanderley</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name><surname>Sant’Anna</surname><given-names>Celso</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff4"/></contrib></contrib-group><aff id="aff1"><institution>Eukaryotic Cell Biology Laboratory (Labio), National Institute of Metrology, Quality and Technology - Inmetro, Duque de Caxias</institution></aff><aff id="aff2"><institution>BioPhenics High-Content Screening Laboratory, Cell and Tissue Imaging Facility (PICT-IBISA), Translational Research Department, PSL Research University</institution></aff><aff id="aff3"><institution>, Post-graduation Program on Translational Biomedicine – Biotrans</institution></aff><aff id="aff4"><institution>Eukaryotic Cell Biology Laboratory (Labio), National Institute of Metrology, Quality and Technology</institution></aff><pub-date date-type="pub" iso-8601-date="2024-04-01" publication-format="electronic"><day>01</day><month>04</month><year>2024</year></pub-date><volume>9</volume><issue>4</issue><issue-title xml:lang="ru"/><fpage>355</fpage><lpage>366</lpage><history><date date-type="received" iso-8601-date="2025-01-15"><day>15</day><month>01</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Bentham Science Publishers</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Bentham Science Publishers</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://journals.eco-vector.com/2405-4615/article/view/646254">https://journals.eco-vector.com/2405-4615/article/view/646254</self-uri><abstract xml:lang="en"><p id="idm46466590294752">Background:Among the various types of cancer, breast cancer is the most incident among women. Due to the resistance to antitumor treatments, alternative treatments have been sought, such as metallic nanoparticles.</p><p id="idm46466590298752">Objective:This study aimed to evaluate the antitumor potential and cytotoxicity induction mechanisms of green synthesized AgCl-NPs and Ag/AgCl-NPs.</p><p id="idm46466590302720">Methods:The antitumor potential of nanoparticles was evaluated in breast cancer BT-474 and MDAMB- 436 cell lines treated with 0-40 μg/mL AgCl-NPs or 0-12.5 μg/mL Ag/AgCl-NPs through imagebased high content analysis method. Normal human retinal pigment epithelial 1 (RPE-1) cells were used for comparison.</p><p id="idm46466590307776">Results:The growth rate of the RPE-1 cells treated with nanoparticles was insignificantly affected, and no significant changes in cell viability were observed. In these cells, the nanoparticle treatments did not induce lysosomal damage, changes in ROS production, or reduction in the mitochondrial membrane potential. The level of BT-474 and MDA-MB-436 cell proliferation was markedly decreased, and cell viability was reduced by 64.19 and 46.19% after treatment with AgCl-NPs and reduced by 98.36 and 82.29% after treatment with Ag/AgCl-NPs. The cells also showed a significant increase in ROS production and loss of mitochondrial membrane potential, which culminated in an increase in the percentage of apoptotic cells. BT-474 cells also presented lysosomal damage when treated with the highest concentrations of both nanoparticle types and actin polymerization was observed after exposure to Ag/AgCl-NPs.</p><p id="idm46466590317152">Conclusions:Together, the results showed overall cytotoxic effects of both AgCl-NPs and Ag/AgCl- NPs towards breast cancer cells with negligible effects against healthy cells, which suggests their promising anticancer and biomedical applications.</p></abstract><kwd-group xml:lang="en"><kwd>Nanoparticles</kwd><kwd>AgCl-NPs</kwd><kwd>Ag/AgCl-NPs</kwd><kwd>breast cancer</kwd><kwd>antitumor</kwd><kwd>HCA.</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73(1): 17-48. doi: 10.3322/caac.21763 PMID: 36633525</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin 2022; 72(6): 524-41. doi: 10.3322/caac.21754 PMID: 36190501</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Kadys A, Gremke N, Schnetter L, Kostev K, Kalder M. Intercontinental comparison of women with breast cancer treated by oncologists in Europe, Asia, and Latin America: A retrospective study of 99,571 patients. J Cancer Res Clin Oncol 2023. doi: 10.1007/s00432-023-04681-7 PMID: 36920565</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Cedolini C, Bertozzi S, Londero AP, et al. Type of breast cancer diagnosis, screening, and survival. Clin Breast Cancer 2014; 14(4): 235-40. doi: 10.1016/j.clbc.2014.02.004 PMID: 24703317</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin 2017; 67(6): 439-48. doi: 10.3322/caac.21412 PMID: 28972651</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Tang Y, Wang Y, Kiani MF, Wang B. Classification, treatment strategy, and associated drug resistance in breast cancer. Clin Breast Cancer 2016; 16(5): 335-43. doi: 10.1016/j.clbc.2016.05.012 PMID: 27268750</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Loibl S, Gianni L. HER2-positive breast cancer. Lancet 2017; 389(10087): 2415-29. doi: 10.1016/S0140-6736(16)32417-5 PMID: 27939064</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Schmadeka R, Harmon BE, Singh M. Triple-negative breast carcinoma: Current and emerging concepts. Am J Clin Pathol 2014; 141(4): 462-77. doi: 10.1309/AJCPQN8GZ8SILKGN PMID: 24619745</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Cardoso F, Costa A, Senkus E, et al. 3rd ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 2017; 28(1): 16-33. doi: 10.1093/annonc/mdw544 PMID: 28177437</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Horton JK, Jagsi R, Woodward WA, Ho A. Breast cancer biology: Clinical implications for breast radiation therapy. Int J Radiat Oncol Biol Phys 2018; 100(1): 23-37. doi: 10.1016/j.ijrobp.2017.08.025 PMID: 29254776</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Kalimutho M, Parsons K, Mittal D, López JA, Srihari S, Khanna KK. Target therapies for triple negative breast cancer: Combating a stubborn. Trends Pharmacol Sci 2015; 36(12): 822-46. doi: 10.1016/j.tips.2015.08.009 PMID: 26538316</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Kindts I, Buelens P, Laenen A, et al. Omitting radiation therapy in women with triple-negative breast cancer leads to worse breast cancer-specific survival. Breast 2017; 32: 18-25. doi: 10.1016/j.breast.2016.12.007 PMID: 28012411</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Samuel P, Pink RC, Caley DP, Currie JMS, Brooks SA, Carter DRF. Over-expression of miR-31 or loss of KCNMA1 leads to increased cisplatin resistance in ovarian cancer cells. Tumour Biol 2016; 37(2): 2565-73. doi: 10.1007/s13277-015-4081-z PMID: 26386726</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Rutberg FG, Dubina MV, Kolikov VA, et al. Effect of silver oxide nanoparticles on tumor growth in vivo. Dokl Biochem Biophys 2008; 421(1): 191-3. doi: 10.1134/S1607672908040078 PMID: 18853769</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Gurunathan S, Raman J, Abd Malek SN, John PA, Vikineswary S. Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: A potential cytotoxic agent against breast cancer cells. Int J Nanomedicine 2013; 8: 4399-413. PMID: 24265551</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arab J Chem 2019; 12(7): 908-31. doi: 10.1016/j.arabjc.2017.05.011</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Kumar I, Mondal M, Sakthivel N. Green synthesis of phytogenic nanoparticles. In: Shukla AK, Iravani S, Eds. Green Synthesis, Characterization and Applications of Nanoparticles. (1st ed.). Amsterdam: Elsevier 2019; pp. 37-73. doi: 10.1016/B978-0-08-102579-6.00003-4</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Vithiya K, Sen S. Biosynthesis of nanoparticles. IJPSR 2011; 2: 2781-5.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Gurunathan S. Rapid biological synthesis of silver nanoparticles and their enhanced antibacterial effects against Escherichia fergusonii and Streptococcus mutans. Arab J Chem 2019; 12(2): 168-80. doi: 10.1016/j.arabjc.2014.11.014</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Namasivayam SKR, Jayakumar D, Kumar VR, et al. Anti bacterial and anti cancerous biocompatible silver nanoparticles synthesized from the cold tolerant strain of spirulina platensis. Res J Pharm Tech 2014; 7: 1404-12.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Thombre R, Mehta S, Mohite J, et al. Synthesis of silver nanoparticles and its cytotoxic effect against thp-1 cancer cell line. Int J Pharm Bio Sci 2013; 4: 184-92.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Husseiny SM, Salah TA, Anter HA. Biosynthesis of size controlled silver nanoparticles by Fusarium oxysporum, their antibacterial and antitumor activities. Beni Suef Univ J Basic Appl Sci 2015; 4(3): 225-31. doi: 10.1016/j.bjbas.2015.07.004</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Nazeema TH, Sugannya PK. Synthesis and characterization of silver nanoparticle from two medicinal plants and its anticancer property. Int J Res Eng Technol 2014; 2: 49-56.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Raman J, Reddy GR, Lakshmanan H, et al. Mycosynthesis and characterization of silver nanoparticles from Pleurotus djamor var. roseus and their in vitro cytotoxicity effect on PC3 cells. Process Biochem 2015; 50(1): 140-7. doi: 10.1016/j.procbio.2014.11.003</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Kang YO, Lee TS, Park WH. Green synthesis and antimicrobial activity of silver chloride nanoparticles stabilized with chitosan oligomer. J Mater Sci Mater Med 2014; 25(12): 2629-38. doi: 10.1007/s10856-014-5294-1 PMID: 25096226</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Gopinath V, Priyadarshini S, Meera Priyadharsshini N, Pandian K, Velusamy P. Biogenic synthesis of antibacterial silver chloride nanoparticles using leaf extracts of Cissus quadrangularis Linn. Mater Lett 2013; 91: 224-7. doi: 10.1016/j.matlet.2012.09.102</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Eugenio M, Müller N, Frasés S, et al. Yeast-derived biosynthesis of silver/silver chloride nanoparticles and their antiproliferative activity against bacteria. RSC Adv 2016; 6(12): 9893-904. doi: 10.1039/C5RA22727E</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Paulkumar K, Rajeshkumar S, Gnanajobitha G, Vanaja M, Malarkodi C, Annadurai G. Biosynthesis of silver chloride nanoparticles using Bacillus subtilis MTCC 3053 and assessment of its antifungal activity. ISRN Nanomater 2013; 2013: 1-8. doi: 10.1155/2013/317963</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Durán N, Nakazato G, Seabra AB. Antimicrobial activity of biogenic silver nanoparticles, and silver chloride nanoparticles: An overview and comments. Appl Microbiol Biotechnol 2016; 100(15): 6555-70. doi: 10.1007/s00253-016-7657-7 PMID: 27289481</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Chankaew C, Somsri S, Tapala W, Mahatheeranont S, Saenjum C, Rujiwatra A. Kaffir lime leaf extract mediated synthesis, anticancer activities and antibacterial kinetics of Ag and Ag/AgCl nanoparticles. Particuology 2018; 40: 160-8. doi: 10.1016/j.partic.2017.11.003</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Eugenio M, Campanati L, Müller N, et al. Silver/silver chloride nanoparticles inhibit the proliferation of human glioblastoma cells. Cytotechnology 2018; 70(6): 1607-18. doi: 10.1007/s10616-018-0253-1 PMID: 30203320</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Gorham PR, Malachlan J, Harmer UT, et al. Isolation and culture of toxic strains of Anabaena flos-aquae (Lingb.). Verh InternatVerein Limnol 1964; 15: 769-80.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>da Silva Ferreira V,. ConzFerreira ME, Lima LMTR, Frasés S, de Souza W, Sant’Anna C. Green production of microalgae-based silver chloride nanoparticles with antimicrobial activity against pathogenic bacteria. Enzyme Microb Technol 2017; 97: 114-21. doi: 10.1016/j.enzmictec.2016.10.018 PMID: 28010768</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Ferreira VS, Eugenio MFC, Dos Santos EDN, et al. Cellular toxicology and mechanism of the response to silver-based nanoparticle exposure in Ewing’s sarcoma cells. Nanotechnology 2021; 32(11): 115101. doi: 10.1088/1361-6528/abcef3 PMID: 33254155</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Lim HK, Gurung RL, Hande MP. DNA-dependent protein kinase modulates the anti-cancer properties of silver nanoparticles in human cancer cells. Mutat Res Genet Toxicol Environ Mutagen 2017; 824: 32-41. doi: 10.1016/j.mrgentox.2017.10.001 PMID: 29150048</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Maity P, Bepari M, Pradhan A, Baral R, Roy S, Maiti Choudhury S. Synthesis and characterization of biogenic metal nanoparticles and its cytotoxicity and anti-neoplasticity through the induction of oxidative stress, mitochondrial dysfunction and apoptosis. Colloids Surf B Biointerfaces 2018; 161: 111-20. doi: 10.1016/j.colsurfb.2017.10.040 PMID: 29055863</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Jadhav K, Deore S, Dhamecha D, et al. Phytosynthesis of silver nanoparticles: Characterization, biocompatibility studies, and anticancer activity. ACS Biomater Sci Eng 2018; 4(3): 892-9. doi: 10.1021/acsbiomaterials.7b00707 PMID: 33418773</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Rodríguez-Razón C, Yañez-Sánchez I, Ramos-Santillan VO, et al. Adhesion, proliferation, and apoptosis in different molecular portraits of breast cancer treated with silver nanoparticles and its pathway-network analysis. Int J Nanomed 2018; 13: 1081-95. doi: 10.2147/IJN.S152237 PMID: 29503542</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Yuan YG, Peng QL, Gurunathan S. Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: Combination therapy for effective cancer treatment. Int J Nanomed 2017; 12: 6487-502. doi: 10.2147/IJN.S135482 PMID: 28919750</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 2009; 3(2): 279-90. doi: 10.1021/nn800596w PMID: 19236062</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Glezer I, Marcourakis T, Avellar MCW, et al. The role of the transcription factor NF-kB in the molecular mechanisms of action of psychoactive drugs. Rev Bras Psiquiatr 2000; 22: 26-30. doi: 10.1590/S1516-44462000000100008</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Manshian BB, Jimenez J, Himmelreich U, Soenen SJ. Presence of an immune system increases anti-tumor effect of Ag nanoparticle treated mice. Adv Healthc Mater 2017; 6(1): 1601099. doi: 10.1002/adhm.201601099 PMID: 27885834</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Yañez-Sánchez I, Carreón-Álvarez CDLL, Velásquez-Ordóñez C, et al. Silver nanoparticles induce apoptosis in L5178Y lymphoma by lipoperoxide activity. Dig J Nanomater Biostruct 2014; 9: 1681-7.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Alberts B. Molecular Biology of the Cell. (4th ed.). Porto Alegre: Artmed 2004; p. 774.</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Loza K, Diendorf J, Sengstock C, et al. The dissolution and biological effects of silver nanoparticles in biological media. J Mater Chem B Mater Biol Med 2014; 2(12): 1634-43. doi: 10.1039/c3tb21569e PMID: 32261391</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Stalin Dhas T, Ganesh Kumar V, Karthick V, Jini Angel K, Govindaraju K. Facile synthesis of silver chloride nanoparticles using marine alga and its antibacterial efficacy. Spectrochim Acta A Mol Biomol Spectrosc 2014; 120: 416-20. doi: 10.1016/j.saa.2013.10.044 PMID: 24211624</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene 2008; 27(50): 6434-51. doi: 10.1038/onc.2008.310 PMID: 18955971</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Xu F, Piett C, Farkas S, Qazzaz M, Syed NI. Silver nanoparticles (AgNPs) cause degeneration of cytoskeleton and disrupt synaptic machinery of cultured cortical neurons. Mol Brain 2013; 6(1): 29. doi: 10.1186/1756-6606-6-29 PMID: 23782671</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Cooper RJ, Spitzer N. Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite dynamics in cultured adult neural stem cells. Neurotoxicology 2015; 48: 231-8. doi: 10.1016/j.neuro.2015.04.008 PMID: 25952507</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Saptarshi SR, Duschl A, Lopata AL. Interaction of nanoparticles with proteins: Relation to bio-reactivity of the nanoparticle. J Nanobiotechnol 2013; 11(1): 26. doi: 10.1186/1477-3155-11-26 PMID: 23870291</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Peretyazhko TS, Zhang Q, Colvin VL. Size-controlled dissolution of silver nanoparticles at neutral and acidic pH conditions: Kinetics and size changes. Environ Sci Technol 2014; 48(20): 11954-61. doi: 10.1021/es5023202 PMID: 25265014</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Swanner J, Mims J, Carroll DL, et al. Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells. Int J Nanomed 2015; 10: 3937-53. PMID: 26185437</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Kato Y, Ozawa S, Miyamoto C, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int 2013; 13(1): 89. doi: 10.1186/1475-2867-13-89 PMID: 24004445</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 2009; 27(1): 76-83. doi: 10.1016/j.biotechadv.2008.09.002 PMID: 18854209</mixed-citation></ref></ref-list></back></article>
