Immobilization of silver nanoparticles in Zr-based MOFs: induction of apoptosis in cancer cells

  • Congcong Han
  • Jian Yang
  • Jinlou Gu
Research Paper


Silver nanoparticles (AgNPs) are a potential class of nanomaterial for antibiosis and chemotherapeutic effects against human carcinoma cells. However, the DNA-damaging ability of free AgNPs pose the critical issues in their biomedical applications. Herein, we demonstrated a facile method to capture Ag+ ions and reduce them into active AgNPs within Zr-based metal-organic frameworks (MOFs) of UiO-66 with a mild reductant of DMF (AgNPs@UiO-66(DMF)). The average diameters of UiO-66 carriers and AgNPs were facilely controlled to be 140 and 10 nm, respectively. The obtained UiO-66 nanocarriers exhibited excellent biocompatibility and could be effectively endocytosed by cancer cells. Additionally, the AgNPs@UiO-66(DMF) could rapidly release Ag+ ions and efficiently inhibit the growth of cancer cells. The half maximal inhibitory concentration (IC50) values of the encapsulated AgNPs were calculated to be 2.7 and 2.45 μg mL−1 for SMMC-7721 and HeLa cells, respectively, which were much lower than those of free AgNPs in the reported works. Therefore, the developed AgNPs@UiO-66(DMF) not only maintained the therapeutic effect against cancer cells but also reduced the dosage of free AgNPs in chemotherapy treatment.

Graphical abstract

A mild reduction process was developed for the fabrication of AgNPs@UiO-66, which exhibited efficient induction of apoptosis in cancer cells.


Metal-organic frameworks Silver nanoparticles Cancer Induction of apoptosis Nanobiomedicine 



This work was financially supported by the Natural Science Foundation of China (51072053, 51372084), the Innovation Program of Shanghai Municipal Education Commission (13zz040), the Nano-Special Foundation for Shanghai Committee of Science and Technology (12 nm0502600), and the 111 Project (B14018).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interest.

Supplementary material

11051_2018_4187_MOESM1_ESM.docx (1.3 mb)
ESM 1 TEM images, Nitrogen adsorption-desorption isotherms, Fluorescence spectra, Flow cytometric analysis, EDS spectrum, Confocal images and the cumulate release profile of Ag+, Table S1 and Table S2. (DOCX 1344 kb)


  1. Ahmed I, Jhung SH (2015) Effective adsorptive removal of indole from model fuel using a metal-organic framework functionalized with amino groups. J Hazard Mater 283:544–550. CrossRefGoogle Scholar
  2. Ahamed M, AlSalhi MS, Siddiqui M (2010) Silver nanoparticle applications and human health. Clin Chim Acta 411(23–24):1841–1848. CrossRefGoogle Scholar
  3. Akhavan O, Abdolahad M, Abdi Y, Mohajerzadeh S (2011) Silver nanoparticles within vertically aligned multi-wall carbon nanotubes with open tips for antibacterial purposes. J Mater Chem 21:387–393. CrossRefGoogle Scholar
  4. AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3:279–290. CrossRefGoogle Scholar
  5. Barreto JC, Smith GS, Strobel NHP, McQuillin PA, Miller TA (1994) Terephthalic acid: a dosimeter for the detection of hydroxyl radicals in vitro. Life Sci 56:PL89–PL96. CrossRefGoogle Scholar
  6. Cavka JH, Jakobsen S, Olsbye U, Guillou N, Lamberti C, Bordiga S, Lillerud KP (2008) A new zirconium inorganic building brick forming metal organic frameworks with exceptional stability. J Am Chem Soc 130(42):13850–13851. CrossRefGoogle Scholar
  7. Chen X, Huang X, Zheng C, Liu Y, Xu T, Liu J (2015) Preparation of different sized nano-silver loaded on functionalized graphene oxide with highly effective antibacterial properties. J Mater Chem B 3:7020–7029. CrossRefGoogle Scholar
  8. Chen X-C, Tao T, Wang Y-G, Peng Y-X, Huang W, Qian H-F (2012) Azo-hydrazone tautomerism observed from UV-vis spectra by pH control and metal-ion complexation for two heterocyclic disperse yellow dyes. Dalton Trans 41:11107–11115. CrossRefGoogle Scholar
  9. Chernousova S, Epple M (2013) Silver as antibacterial agent: ion, nanoparticle, and metal. Angew Chem Int Ed 52(6):1636–1653. CrossRefGoogle Scholar
  10. Deng K, Hou Z, Li X, Li C, Zhang Y, Deng X, Cheng Z, Lin J (2015) Aptamer-mediated up-conversion core/MOF shell nanocomposites for targeted drug delivery and cell imaging. Sci Rep 5(7851).
  11. Ehdaie B (2007) Application of nanotechnology in cancer research: review of progress in the National Cancer Institute’s Alliance for Nanotechnology. Int J Biol Sci 3(2):108–110CrossRefGoogle Scholar
  12. Feng Q, Wu J, Chen G, Cui F, Kim T, Kim J (2000) A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res 52(4):662–668CrossRefGoogle Scholar
  13. Férey G (2008) Hybrid porous solids: past, present, future. Chem Soc Rev 37(1):191–214. CrossRefGoogle Scholar
  14. Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5:161–171. CrossRefGoogle Scholar
  15. Foldbjerg R, Dang DA, Autrup H (2011) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85(7):743–750. CrossRefGoogle Scholar
  16. Gong C, Shen Y, Chen J, Song Y, Chen S, Song Y, Wang L (2017) Microperoxidase-11@PCN-333 (Al)/three-dimensional macroporous carbon electrode for sensing hydrogen peroxide. Sens Actuators, B: Chemical 239:890–897. CrossRefGoogle Scholar
  17. Gopinath P, Gogoi SK, Sanpui P, Paul A, Chattopadhyay A, Ghosh SS (2010) Signaling gene cascade in silver nanoparticle induced apoptosis. Colloids Surf, B 77(2):240–245. CrossRefGoogle Scholar
  18. Gurunathan S, Han JW, Dayem AA, Eppakayala V, Park JH, Cho SG, Lee KJ, Kim JH (2013) Green synthesis of anisotropic silver nanoparticles and its potential cytotoxicity in human breast cancer cells (MCF-7). J Ind Eng Chem 19:1600–1605. CrossRefGoogle Scholar
  19. He Y, du, Tang, Zheng, Zhang, Zhao, Lv, Qianfa J (2013) Green synthesis of silver nanoparticles by Chrysanthemum morifolium Ramat. Extract and their application in clinical ultrasound gel. Int J Nanomedicine 8:1809–1815. CrossRefGoogle Scholar
  20. Hsin Y-H, Chen C-F, Huang S, Shih T-S, Lai P-S, Chueh PJ (2008) The apoptotic effect of nanosilver is mediated by a ROS-and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett 179(3):130–139. CrossRefGoogle Scholar
  21. Igaz N, Kovács D, Rázga Z, Kónya Z, Boros IM, Kiricsi M (2016) Modulating chromatin structure and DNA accessibility by deacetylase inhibition enhances the anti-cancer activity of silver nanoparticles. Colloids Surf B: Biointerfaces 146:670–677. CrossRefGoogle Scholar
  22. Jeyaraj M, Rajesh M, Arun R, MubarakAli D, Sathishkumar G, Sivanandhan G, Dev GK, Manickavasagam M, Premkumar K, Thajuddin N, Ganapathi A (2013) An investigation on the cytotoxicity and caspase-mediated apoptotic effect of biologically synthesized silver nanoparticles using Podophyllum hexandrum on human cervical carcinoma cells. Colloids Surf B 102:708–717. CrossRefGoogle Scholar
  23. Jose Ruben M, Jose Luis E, Alejandra C, Katherine H, Juan BK, Jose Tapia R, Miguel Jose Y (2005) The bactericidal effect of silver nanoparticles. Nanotechnology 16(10):2346–2353CrossRefGoogle Scholar
  24. Kathiravan V, Ravi S, Ashokkumar S (2014) Synthesis of silver nanoparticles from Melia dubia leaf extract and their in vitro anticancer activity. Spectrochim Acta A 130(15):116–121. CrossRefGoogle Scholar
  25. Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, Kim SH, Park YK, Park YH, Hwang CY, Kim YK, Lee YS, Jeong DH, Cho MH (2007) Antimicrobial effects of silver nanoparticles. Nanomedicine 3(1):95–101. CrossRefGoogle Scholar
  26. Kim J, Yeo S, Jeon J-D, Kwak S-Y (2015) Enhancement of hydrogen storage capacity and hydrostability of metal–organic frameworks (MOFs) with surface-loaded platinum nanoparticles and carbon black. Microporous Mesoporous Mater 202:8–15. CrossRefGoogle Scholar
  27. Kitagawa S, Kitaura R, Si N (2004) Functional porous coordination polymers. Angew Chem Int Ed 43(18):2334–2375. CrossRefGoogle Scholar
  28. Kovács D, Szőke K, Igaz N, Spengler G, Molnár J, Tóth T, Madarász D, Rázga Z, Kónya Z, Boros IM, Kiricsi M (2016) Silver nanoparticles modulate ABC transporter activity and enhance chemotherapy in multidrug resistant cancer. Nanomedicine 12:601–610. CrossRefGoogle Scholar
  29. Liu J, Sonshine DA, Shervani S, Hurt RH (2010) Controlled release of biologically active silver from nanosilver surfaces. ACS Nano 4:6903–6913. CrossRefGoogle Scholar
  30. Manikandan R, Manikandan B, Raman T, Arunagirinathan K, Prabhu NM, Jothi Basu M, Perumal M, Palanisamy S, Munusamy A (2015) Biosynthesis of silver nanoparticles using ethanolic petals extract of Rosa indica and characterization of its antibacterial, anticancer and anti-inflammatory activities. Spectrochim Acta A 138:120–129. CrossRefGoogle Scholar
  31. Marudhupandi T, Ajith Kumar TT, Lakshmanasenthil S, Suja G, Vinothkumar T (2015) In vitro anticancer activity of fucoidan from Turbinaria conoides against A549 cell lines. Int J Biol Macromol 72:919–923. CrossRefGoogle Scholar
  32. Orellana-Tavra C, Baxter EF, Tian T, Bennett TD, Slater NK, Cheetham AK, Fairen-Jimenez D (2015) Amorphous metal–organic frameworks for drug delivery. Chem Commun 51(73):13878–13881. CrossRefGoogle Scholar
  33. Pu S, Xu L, Sun L, Du H (2015) Tuning the optical properties of the zirconium–UiO-66 metal–organic framework for photocatalytic degradation of methyl orange Inorg. Chem Commun 52:50–52. Google Scholar
  34. Sanpui P, Chattopadhyay A, Ghosh SS (2011) Induction of apoptosis in cancer cells at low silver nanoparticle concentrations using chitosan nanocarrier. ACS Appl Mater Interfaces 3(2):218–228. CrossRefGoogle Scholar
  35. Sarkar K, Banerjee SL, Kundu PP, Madras G, Chatterjee K (2015) Biofunctionalized surface-modified silver nanoparticles for gene delivery. J Mat Chem B 3(26):5266–5276. CrossRefGoogle Scholar
  36. Schaate A, Roy P, Godt A, Lippke J, Waltz F, Wiebcke M, Behrens P (2011) Modulated synthesis of Zr-based metal–organic frameworks: from nano to single crystals. ChemEur J 17(24):6643–6651. Google Scholar
  37. Shen L, Liang R, Luo M, Jing F, Wu L (2015) Electronic effects of ligand substitution on metal-organic framework photocatalysts: the case study of UiO-66 Phys. Chem Chem Phys 17:117–121. CrossRefGoogle Scholar
  38. Sen Karaman D et al (2016) Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation. J Mat Chem B 4(19):3292–3304. CrossRefGoogle Scholar
  39. Singh RP, Ramarao P (2012) Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles. Toxicol Lett 213:249–259. CrossRefGoogle Scholar
  40. Sondi I, Salopek-Sondi B (2004) Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. J Colloid Interface Sci 275(1):177–182. CrossRefGoogle Scholar
  41. Song Y, Chen J, Liu H, Song Y, Xu F, Tan H, Wang L (2015a) Conformation, bioactivity and electrochemical performance of glucose oxidase immobilized on surface of gold nanoparticles. Electrochim Acta 158:56–63. CrossRefGoogle Scholar
  42. Song Y, Wei C, He J, Li X, Lu X, Wang L (2015b) Porous co nanobeads/rGO nanocomposites derived from rGO/co-metal organic frameworks for glucose sensing. Sensors Actuators B 220:1056–1063. CrossRefGoogle Scholar
  43. Sotiriou GA, Pratsinis SE (2010) Antibacterial activity of nanosilver ions and particles. Environ Sci Technol 44:5649–5654. CrossRefGoogle Scholar
  44. Sriram MI, Kanth SBM, Kalishwaralal K, Gurunathan S (2010) Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model. Int J Nanomedicine 5:753–762. Google Scholar
  45. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267(5203):1456–1462. CrossRefGoogle Scholar
  46. Wang J, Chen D, Li B, He J, Duan D, Shao D, Nie M (2016) Fe-MIL-101 exhibits selective cytotoxicity and inhibition of angiogenesis in ovarian cancer cells via downregulation of MMP. Sci Rep 6:26126. CrossRefGoogle Scholar
  47. Wei L, Lu J, Xu H, Patel A, Chen Z-S, Chen G (2015) Silver nanoparticles: synthesis, properties, and therapeutic applications. Drug Discov Today 20(5):595–601. CrossRefGoogle Scholar
  48. Xia QH, Ma YJ, Wang JW (2016) Biosynthesis of silver nanoparticles using Taxus yunnanensis Callus and their antibacterial activity and cytotoxicity in human cancer cells. Nano 6(9):160. Google Scholar
  49. Xiong R, Lu C, Wang Y, Zhou Z, Zhang X (2013) Nanofibrillated cellulose as the support and reductant for the facile synthesis of Fe3O4/Ag nanocomposites with catalytic and antibacterial activity. J Mat Chem A 1(47):14910–14918. CrossRefGoogle Scholar
  50. Xiu Z-m, Zhang Q-b, Puppala HL, Colvin VL, Alvarez PJ (2012) Negligible particle-specific antibacterial activity of silver nanoparticles. Nano Lett 12(8):4271–4275. CrossRefGoogle Scholar
  51. Xu W-X, Li J, Liu R-P, Zhou W-X, Ma W-Y, Zhang F-X (2013) A novel 1D linear zinc(II) coordination polymer based 2, 2′-bipyridine-4, 4′-dicarboxylic acid: synthesis, crystal structure and photoluminescence property. Inorganic Chem Commun 28:12–15. CrossRefGoogle Scholar
  52. Yaghi OM, O'Keeffe M, Ockwig NW, Chae HK, Eddaoudi M, Kim J (2003) Reticular synthesis and the design of new materials. Nature 423:705–714. CrossRefGoogle Scholar
  53. Yang J, Chen X, Li Y, Zhuang Q, Liu P, Gu J (2017a) Zr-based MOFs shielded with phospholipid bilayers: improved biostability and cell uptake for biological applications. Chem Mater 29(10):4580–4589. CrossRefGoogle Scholar
  54. Yang X, Li L, He D, Hai L, Tang J, Li H, He X, Wang K (2017b) A metal-organic framework based nanocomposite with co-encapsulation of Pd@Au nanoparticles and doxorubicin for pH- and NIR-triggered synergistic chemo-photothermal treatment of cancer cells. J Mater Chem B 5(24):4648–4659. CrossRefGoogle Scholar
  55. Yezhelyev MV, Gao X, Xing Y, Al-Hajj A, Nie S, O'Regan RM (2006) Emerging use of nanoparticles in diagnosis and treatment of breast cancer. The Lancet Oncology 7:657–667. CrossRefGoogle Scholar
  56. Wang H, Yuan X, Zeng G, Wu Y, Liu Y, Jiang Q, Gu S (2015) Three dimensional graphene based materials: synthesis and applications from energy storage and conversion to electrochemical sensor and environmental remediation. Adv Colloid Interf Sci 221:41–59. CrossRefGoogle Scholar
  57. Wang S, Li G, Huo Q, Liu Y (2013) Syntheses, crystal structures of two coordination polymers constructed from imidazole-based dicarboxylate ligands containing alkyl group. Inorg Chem Commun 30:115–119. CrossRefGoogle Scholar
  58. Zhan H, Zhou X, Cao Y, Jagtiani T, Chang T-L, Liang JF (2017) Anti-cancer activity of camptothecin nanocrystals decorated by silver nanoparticles. J Mater Chem B 5(14):2692–2701. CrossRefGoogle Scholar
  59. Zhang Z, Miao L, Lv C, Sun H, Wei S, Wang B, Huang C, Jiao B (2013) Wentilactone B induces G2/M phase arrest and apoptosis via the Ras/Raf/MAPK signaling pathway in human hepatoma SMMC-7721 cells. Cell Death & Dis 4(6):e657. CrossRefGoogle Scholar
  60. Zhao H-X, Zou Q, Sun S-K, Yu C, Zhang X, Li R-J, Fu Y-Y (2016) Theranostic metal-organic framework core-shell composites for magnetic resonance imaging and drug delivery. Chem Sci 7(8):5294–5301. CrossRefGoogle Scholar
  61. Zhu X, Gu J, Wang Y, Li B, Li Y, Zhao W, Shi J (2014) Inherent anchorages in UiO-66 nanoparticles for efficient capture of alendronate and its mediated release. Chem Commun 50(63):8779–8782. CrossRefGoogle Scholar

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and EngineeringEast China University of Science and TechnologyShanghaiChina

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