Inhibition of cancer cells using target-specific 2A3 antibody-conjugated gold nanoclusters
Abstract
Background: Metal nanoclusters (NCs) with outstanding structural and optical properties have been intensively validated for applications in nanomedicine and nanotechnology. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in many cancer cells.
Objective: The gold nanoclusters conjugated with a single domain antibody targeting CEACAM6 of 2A3 (2A3-AuNCs) were synthesized for the inhibition of cancer cells.
Methods: 2A3-AuNCs were prepared via a facile hydrothermal approach. The cell viability was measured by resazurin dye reduction assay. The cell death was analyzed by fluorescence imaging.
Results: Structural and optical characterizations demonstrated the successful synthesis of 2A3-AuNCs with a roughly spherical shape and a size of 2.35 nm. The 2A3-AuNCs revealed a maximum fluorescence intensity at 350 nm with a fluorescence quantum yield of 4.0%. The cell viability assay indicated that 2A3-AuNCs could inhibit the growths of cancer cells with overexpressed CEACAM6, including breast cancer MDA-MB-231 and MDA-MB-468 cells. The fluorescence imaging results also demonstrated that 2A3-AuNCs could inhibit the growth of cancer cells with MDA-MB-231 and MDA-MB-468 cells.
Conclusion: Combination with the results of cell viability assay and fluorescence imaging, the surface ligand of 2A3 antibody on 2A3-AuNCs exhibited promising inhibition of CEACAM6 overexpressed cancer cells. Our work provides a potential application of AuNCs in cancer therapy.
References
Yougbaré S, Chou H-L, Yang C-H, Krisnawati DI, Jazidie A, Nuh M, et al. Facet-dependent gold nanocrystals for effective photothermal killing of bacteria. J Hazard Mater. 2021;407: 124617. https://doi.org/10.1016/j.jhazmat.2020.124617
Li C-H, Kuo T-R, Su H-J, Lai W-Y, Yang P-C, Chen J-S, et al. Fluorescence-guided probes of aptamer-targeted gold nanoparticles with computed tomography imaging accesses for in vivo tumor resection. Sci Rep. 2015;5: 15675. https://doi.org/10.1038/srep15675
Mutalik C, Hsiao Y-C, Chang Y-H, Krisnawati DI, Alimansur M, Jazidie A, et al. High UV-VIS-NIR light-induced antibacterial activity by heterostructured TiO2-FeS2 nanocomposites. Int J Nanomedicine. 2020;15: 8911. https://doi.org/10.2147/IJN.S282689
Kuo T-R, Liao H-J, Chen Y-T, Wei C-Y, Chang C-C, Chen Y-C, et al. Extended visible to near-infrared harvesting of earth-abundant FeS2-TiO2 heterostructures for highly active photocatalytic hydrogen evolution. Green Chem. 2018;20: 1640-7. https://doi.org/10.1039/C7GC03173D
Zhu YP, Kuo TR, Li YH, Qi MY, Chen G, Wang JL, et al. Emerging dynamic structure of electrocatalysts unveiled by in situ X-ray diffraction/absorption spectroscopy. Energy Environ Sci. 2021;14: 1928-58. https://doi.org/10.1039/d0ee03903a
Tung CW, Kuo TR, Hsu CS, Chuang Y, Chen HC, Chang CK, et al. Light-Induced Activation of Adaptive Junction for Efficient Solar-Driven Oxygen Evolution: In Situ Unraveling the Interfacial Metal-Silicon Junction. Adv Energy Mater. 2019;9: 1901308. https://doi.org/10.1002/aenm.201901308
Yougbare S, Mutalik C, Krisnawati DI, Kristanto H, Jazidie A, Nuh M, et al. Nanomaterials for the Photothermal Killing of Bacteria. Nanomaterials. 2020;10: 1123. https://doi.org/10.3390/nano10061123
Wang J, Tan HY, Kuo TR, Lin SC, Hsu CS, Zhu Y, et al. In situ identifying the dynamic structure behind activity of atomically dispersed platinum catalyst toward hydrogen evolution reaction. Small. 2021;17: 2005713. https://doi.org/10.1002/smll.202005713
Yougbaré S, Mutalik C, Chung P-F, Krisnawati DI, Rinawati F, Irawan H, et al. Gold nanorod-decorated metallic MoS2 nanosheets for synergistic photothermal and photodynamic antibacterial therapy. Nanomaterials. 2021;11: 3064. https://doi.org/10.3390/nano11113064
Tan S-H, Yougbaré S, Tao H-Y, Chang C-C, Kuo T-R. Plasmonic gold nanoisland film for bacterial theranostics. Nanomaterials. 2021;11: 3139. https://doi.org/10.3390/nano11113139
Mutalik C, Okoro G, Krisnawati DI, Jazidie A, Rahmawati EQ, Rahayu D, et al. Copper sulfide with morphology-dependent photodynamic and photothermal antibacterial activities. J Colloid Interface Sci. 2022;607: 1825-35. https://doi.org/10.1016/j.jcis.2021.10.019
Yougbare S, Mutalik C, Okoro G, Lin IH, Krisnawati DI, Jazidie A, et al. Emerging Trends in Nanomaterials for Antibacterial Applications. Int J Nanomedicine. 2021;16: 5831-67. https://doi.org/10.2147/ijn.s328767
Mutalik C, Krisnawati DI, Patil SB, Khafid M, Atmojo DS, Santoso P, et al. Phase-dependent MoS2 nanoflowers for light-driven antibacterial application. ACS Sustain Chem Eng. 2021;9: 7904-12. https://doi.org/10.1021/acssuschemeng.1c01868
Mutalik C, Wang DY, Krisnawati DI, Jazidie A, Yougbare S, Kuo TR. Light-Activated Heterostructured Nanomaterials for Antibacterial Applications. Nanomaterials. 2020;10: 643. https://doi.org/10.3390/nano10040643
Tan S-H, Yougbaré S, Chu H-L, Kuo T-R, Cheng T-M. Hemoglobin-Conjugated Gold Nanoclusters for Qualitative Analysis of Haptoglobin Phenotypes. Polymers. 2020;12: 2242. https://doi.org/10.3390/polym12102242
Du YX, Sheng HT, Astruc D, Zhu MZ. Atomically Precise Noble Metal Nanoclusters as Efficient Catalysts: A Bridge between Structure and Properties. Chem Rev. 2020;120: 526-622. https://doi.org/10.1021/acs.chemrev.8b00726
Kang X, Zhu MZ. Tailoring the photoluminescence of atomically precise nanoclusters. Chem Soc Rev. 2019;48: 2422-57. https://doi.org/10.1039/c8cs00800k
Kaur N, Aditya RN, Singh A, Kuo TR. Biomedical Applications for Gold Nanoclusters: Recent Developments and Future Perspectives. Nanoscale Res Lett. 2018;13: 302. https://doi.org/10.1186/s11671-018-2725-9
Cheng TM, Chu HL, Lee YC, Wang DY, Chang CC, Chung KL, et al. Quantitative Analysis of Glucose Metabolic Cleavage in Glucose Transporters Overexpressed Cancer Cells by Target-Specific Fluorescent Gold Nanoclusters. Anal Chem. 2018;90: 3974-80. https://doi.org/10.1021/acs.analchem.7b04961
Krisnawati DI, Hsu P-H, Lin Y-H, Alimansur M, Atmojo DS, Rahmawati EQ, et al. The Use of the ROS Scavenger Cysteine as a Surface Ligand of Metal Nanoclusters and Its Bactericidal Elimination Effect. Applied Sciences. 2021;11: 4095. https://doi.org/10.3390/app11094095
Hsu P-H, Yougbaré S, Kuo J-C, Krisnawati DI, Jazidie A, Nuh M, et al. One-pot synthesis of thiol-modified liquid crystals conjugated fluorescent gold nanoclusters. Nanomaterials. 2020;10: 1755. https://doi.org/10.3390/nano10091755
Jia X, Li J, Han L, Ren J, Yang X, Wang E. DNA-hosted copper nanoclusters for fluorescent identification of single nucleotide polymorphisms. Acs Nano. 2012;6: 3311-7. https://doi.org/10.1021/nn3002455
Yougbare S, Chang T-K, Tan S-H, Kuo J-C, Hsu P-H, Su C-Y, et al. Antimicrobial gold nanoclusters: recent developments and future perspectives. Int J Mol Sci. 2019;20: 2924. https://doi.org/10.3390/ijms20122924
Zhou M, Higaki T, Hu GX, Sfeir MY, Chen YX, Jiang DE, et al. Three-orders-of-magnitude variation of carrier lifetimes with crystal phase of gold nanoclusters. Science. 2019;364: 279-82. https://doi.org/10.1126/science.aaw8007
Chen TK, Lin HB, Cao YT, Yao QF, Xie JP. Interactions of Metal Nanoclusters with Light: Fundamentals and Applications. Adv Mater. 2103918. https://doi.org/10.1002/adma.202103918
Zheng K, Setyawati MI, Leong DT, Xie J. Antimicrobial gold nanoclusters. ACS nano. 2017;11: 6904-10. https://doi.org/10.1021/acsnano.7b02035
Chang T-K, Cheng T-M, Chu H-L, Tan S-H, Kuo J-C, Hsu P-H, et al. Metabolic mechanism investigation of antibacterial active cysteine-conjugated gold nanoclusters in escherichia coli. ACS Sustain Chem Eng. 2019;7: 15479-86. https://doi.org/10.1021/acssuschemeng.9b03048
Wang S, Wang Y, Peng Y, Yang X. Exploring the antibacteria performance of multicolor Ag, Au, and Cu nanoclusters. ACS Appl Mater Interfaces. 2019;11: 8461-9. https://doi.org/10.1021/acsami.8b22143
Kuo J-C, Tan S-H, Hsiao Y-C, Mutalik C, Chen H-M, Yougbaré S, et al. Unveiling the Antibacterial Mechanism of Gold Nanoclusters via In Situ Transmission Electron Microscopy. ACS Sustain Chem Eng. 2021;10: 464-71. https://doi.org/10.1021/acssuschemeng.1c06714
Cheng T-M, Murad YM, Chang C-C, Yang M-C, Baral TN, Cowan A, et al. Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells. European Journal of Cancer. 2014;50: 713-21. https://doi.org/10.1016/j.ejca.2012.07.019
Shang L, Dong S, Nienhaus GU. Ultra-small fluorescent metal nanoclusters: synthesis and biological applications. Nano Today. 2011;6: 401-18. https://doi.org/10.1016/j.nantod.2011.06.004
Luo Z, Yuan X, Yu Y, Zhang Q, Leong DT, Lee JY, et al. From Aggregation-Induced Emission of Au(I)–Thiolate Complexes to Ultrabright Au(0)@Au(I)–Thiolate Core–Shell Nanoclusters. J Am Chem Soc. 2012;134: 16662-70. https://doi.org/10.1021/ja306199p
Goswami N, Yao QF, Luo ZT, Li JG, Chen TK, Xie JP. Luminescent Metal Nanoclusters with Aggregation-Induced Emission. J Phys Chem Lett. 2016;7: 962-75. https://doi.org/10.1021/acs.jpclett.5b02765
Bera D, Goswami N. Driving Forces and Routes for Aggregation-Induced Emission-Based Highly Luminescent Metal Nanocluster Assembly. J Phys Chem Lett. 2021;12: 9033-46. https://doi.org/10.1021/acs.jpclett.1c02406
Copyright (c) 2022 Authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
