Generic placeholder image

Current Nanomaterials


ISSN (Print): 2405-4615
ISSN (Online): 2405-4623

Research Article

Quantitative Characterization of the Effect of Biogenic silver-based Nanoparticles on Breast Cancer Cells by High Content Analysis

Author(s): Veronica Ferreira, Mateus Eugenio, Elaine Del Nery, Wanderley de Souza and Celso Sant’Anna*

Volume 9, Issue 4, 2024

Published on: 20 September, 2023

Page: [355 - 366] Pages: 12

DOI: 10.2174/2405461508666230816090519

Price: $65


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.

Objective: This study aimed to evaluate the antitumor potential and cytotoxicity induction mechanisms of green synthesized AgCl-NPs and Ag/AgCl-NPs.

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.

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.

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.

Keywords: Nanoparticles, AgCl-NPs, Ag/AgCl-NPs, breast cancer, antitumor, HCA.

Graphical Abstract
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73(1): 17-48.
[] [PMID: 36633525]
Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin 2022; 72(6): 524-41.
[] [PMID: 36190501]
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.
[] [PMID: 36920565]
Cedolini C, Bertozzi S, Londero AP, et al. Type of breast cancer diagnosis, screening, and survival. Clin Breast Cancer 2014; 14(4): 235-40.
[] [PMID: 24703317]
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.
[] [PMID: 28972651]
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.
[] [PMID: 27268750]
Loibl S, Gianni L. HER2-positive breast cancer. Lancet 2017; 389(10087): 2415-29.
[] [PMID: 27939064]
Schmadeka R, Harmon BE, Singh M. Triple-negative breast carcinoma: Current and emerging concepts. Am J Clin Pathol 2014; 141(4): 462-77.
[] [PMID: 24619745]
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.
[] [PMID: 28177437]
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.
[] [PMID: 29254776]
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.
[] [PMID: 26538316]
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.
[] [PMID: 28012411]
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.
[] [PMID: 26386726]
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.
[] [PMID: 18853769]
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]
Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arab J Chem 2019; 12(7): 908-31.
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.
Vithiya K, Sen S. Biosynthesis of nanoparticles. IJPSR 2011; 2: 2781-5.
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.
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.
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.
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.
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.
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.
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.
[] [PMID: 25096226]
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.
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.
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.
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.
[] [PMID: 27289481]
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.
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.
[] [PMID: 30203320]
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.
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.
[] [PMID: 28010768]
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.
[] [PMID: 33254155]
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.
[] [PMID: 29150048]
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.
[] [PMID: 29055863]
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.
[] [PMID: 33418773]
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.
[] [PMID: 29503542]
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.
[] [PMID: 28919750]
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.
[] [PMID: 19236062]
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.
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.
[] [PMID: 27885834]
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.
Alberts B. Molecular Biology of the Cell. (4th ed.). Porto Alegre: Artmed 2004; p. 774.
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.
[] [PMID: 32261391]
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.
[] [PMID: 24211624]
Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene 2008; 27(50): 6434-51.
[] [PMID: 18955971]
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.
[] [PMID: 23782671]
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.
[] [PMID: 25952507]
Saptarshi SR, Duschl A, Lopata AL. Interaction of nanoparticles with proteins: Relation to bio-reactivity of the nanoparticle. J Nanobiotechnol 2013; 11(1): 26.
[] [PMID: 23870291]
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.
[] [PMID: 25265014]
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]
Kato Y, Ozawa S, Miyamoto C, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int 2013; 13(1): 89.
[] [PMID: 24004445]
Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 2009; 27(1): 76-83.
[] [PMID: 18854209]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy