Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Synthesis of hydrogels incorporating core–shell structured Fe3O4@ZIF-8 as bio-nanocomposite carriers for drug delivery

Pagasukon Mekrattanachai https://orcid.org/0000-0002-3374-0254 A , Naruemon Setthaya A , Chakkresit Chindawong A , Bunlawee Yotnoi A , Wei Guo Song B and Chawan Manaspon https://orcid.org/0000-0001-8961-7901 C *
+ Author Affiliations
- Author Affiliations

A School of Chemistry, Faculty of Science, University of Phayao, 19 Moo 2, Maeka, Muang District, Phayao, 56000, Thailand.

B Beijing National Laboratory for Molecular Sciences, Laboratory of Molecular Nanostructures and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

C Biomedical Engineering Institute, Chiang Mai University, 239 Huay Kaew Road, Muang District, Chiang Mai, 50200, Thailand.

* Correspondence to: chawan.m@cmu.ac.th

Handling Editor: Stuart Batten

Australian Journal of Chemistry 76(4) 201-208 https://doi.org/10.1071/CH22224
Submitted: 21 October 2022  Accepted: 25 May 2023   Published: 15 June 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing.

Abstract

Due to its high porosity and excellent pH-sensitive breakdown, the zeolitic imidazolate framework-8 (ZIF-8) has been investigated as a drug delivery vehicle. To increase the magnetic property of ZIF-8 nanoparticles, Fe3O4 nanoparticles (Fe3O4 NPs) were encapsulated to form a core–shell structure (Fe3O4@ZIF-8). The core–shell particles were then incorporated into a hydrogel to increase biocompatibility. The Fe3O4@ZIF-8-incorporated hydrogel nanocomposite (Fe3O4@ZIF-8 hydrogel) was then studied for in vitro cytotoxicity for drug delivery applications. Transmission electron microscopy images confirmed the core–shell structure of the synthesized Fe3O4@ZIF-8 with a central Fe3O4 core and a shell of nano-sized ZIF-8. The specific surface area of the obtained Fe3O4@ZIF-8 was 821 m2 g–1 with a pore volume of 0.36 cm3 g–1. The effect of the prepared Fe3O4@ZIF-8 on cell viability (mouse fibroblast, L929 cell line) was investigated using an MTT (3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide) assay. The Fe3O4@ZIF-8 and pure ZIF-8 showed a 50% inhibitory concentration at 28.2 + 1.0 and 11.2 + 6.6 µg mL–1, respectively. A chitosan/pluronic F-127 hydrogel incorporating Fe3O4@ZIF-8 was successfully prepared and showed over 75% cell viability compared to the fresh culture medium. Overall results indicated the safety of using chitosan/pluronic F-127 vehicles containing Fe3O4@ZIF-8 as a carrier for drug delivery systems.

Keywords: biocompatibility, core-shell structure, drug delivery system, Fe3O4 particles, hydrogels, metal–organic frameworks, nanocomposite, ZIF-8.


References

[1]  MP Suh, HJ Park, TK Prasad, DW Lim, Hydrogen storage in metal–organic frameworks. Chem Rev 2012, 112, 782.
         | Hydrogen storage in metal–organic frameworks.Crossref | GoogleScholarGoogle Scholar |

[2]  P Mekrattanachai, L Zhu, N Setthaya, C Chindawong, WG Song, The highly effective cobalt based metal–organic frameworks catalyst for one pot oxidative esterification under mild conditions. Catal Lett 2022, 152, 1639.
         | The highly effective cobalt based metal–organic frameworks catalyst for one pot oxidative esterification under mild conditions.Crossref | GoogleScholarGoogle Scholar |

[3]  Q Zhu, Y Li, W Wang, G Sun, K Yan, D Wang, High performance HKUST-1@PVA-co-PE/PVA hybrid hydrogel with enhanced selective adsorption. Compos Commun 2018, 10, 36.
         | High performance HKUST-1@PVA-co-PE/PVA hybrid hydrogel with enhanced selective adsorption.Crossref | GoogleScholarGoogle Scholar |

[4]  Q Jia, Z Li, C Guo, X Huang, Y Song, N Zhou, M Wang, Z Zhang, L He, M Du, A γ-cyclodextrin-based metal–organic framework embedded with graphene quantum dots and modified with PEGMA via SI-ATRP for anticancer drug delivery and therapy. Nanoscale 2019, 11, 20956.
         | A γ-cyclodextrin-based metal–organic framework embedded with graphene quantum dots and modified with PEGMA via SI-ATRP for anticancer drug delivery and therapy.Crossref | GoogleScholarGoogle Scholar |

[5]  S Beg, M Rahman, A Jain, S Saini, P Midoux, C Pichon, FJ Ahmad, S Akhter, Nanoporous metal organic frameworks as hybrid polymer–metal composites for drug delivery and biomedical applications. Drug Discov Today 2017, 22, 625.
         | Nanoporous metal organic frameworks as hybrid polymer–metal composites for drug delivery and biomedical applications.Crossref | GoogleScholarGoogle Scholar |

[6]  J Della Rocca, D Liu, W Lin, Nanoscale metal–organic frameworks for biomedical imaging and drug delivery. Acc Chem Res 2011, 44, 957.
         | Nanoscale metal–organic frameworks for biomedical imaging and drug delivery.Crossref | GoogleScholarGoogle Scholar |

[7]  LC Gonçalves, AB Seabra, MT Pelegrino, DR de Araujo, JS Bernardes, PS Haddad, Superparamagnetic iron oxide nanoparticles dispersed in Pluronic F127 hydrogel: potential uses in topical applications. RSC Adv 2017, 7, 14496.
         | Superparamagnetic iron oxide nanoparticles dispersed in Pluronic F127 hydrogel: potential uses in topical applications.Crossref | GoogleScholarGoogle Scholar |

[8]  R Ettlinger, N Moreno, N Ziółkowska, A Ullrich, H-A Krug von Nidda, D Jirák, K Kerl, H Bunzen, In vitro studies of Fe3O4-ZIF-8 core–shell nanoparticles designed as potential theragnostics. Part Part Syst Charact 2020, 37, 2000185.
         | In vitro studies of Fe3O4-ZIF-8 core–shell nanoparticles designed as potential theragnostics.Crossref | GoogleScholarGoogle Scholar |

[9]  G Ju,, B Liu, M Ji, R Jin, X Xu, Y Xiao, J Li, D Xu, Y Huang, J Hou, Folic acid–modified miR-491-5p–Loaded ZIF-8 nanoparticles inhibit castration-resistant prostate cancer by regulating the expression of EPHX1. Front Bioeng Biotechnol 2021, 9, 706536.
         | Folic acid–modified miR-491-5p–Loaded ZIF-8 nanoparticles inhibit castration-resistant prostate cancer by regulating the expression of EPHX1.Crossref | GoogleScholarGoogle Scholar |

[10]  L Wu, W Wen, X Wang, D Huang, J Cao, X Qi, S Shen, Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs. Part Fibre Toxicol 2022, 24, 24.
         | Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs.Crossref | GoogleScholarGoogle Scholar |

[11]  C Cheng, C Li, X Zhu, W Han, J Li, Y Lv, Doxorubicin-loaded Fe3O4-ZIF-8 nano-composites for hepatocellular carcinoma therapy. J Biomater Appl 2019, 33, 1373.
         | Doxorubicin-loaded Fe3O4-ZIF-8 nano-composites for hepatocellular carcinoma therapy.Crossref | GoogleScholarGoogle Scholar |

[12]  H-X Zhao, Q Zou, S-K Sun, C Yu, X Zhang, R-J Li, Y-Y Fu, Theranostic metal–organic framework core–shell composites for magnetic resonance imaging and drug delivery. Chem Sci 2016, 7, 5294.
         | Theranostic metal–organic framework core–shell composites for magnetic resonance imaging and drug delivery.Crossref | GoogleScholarGoogle Scholar |

[13]  G Wang, L Jin, Y Dong, L Niu, Y Liu, F Ren, X Su, Multifunctional Fe3O4-CdTe@SiO2-carboxymethyl chitosan drug nanocarriers: synergistic effect towards magnetic targeted drug delivery and cell imaging. New J Chem 2014, 38, 700.
         | Multifunctional Fe3O4-CdTe@SiO2-carboxymethyl chitosan drug nanocarriers: synergistic effect towards magnetic targeted drug delivery and cell imaging.Crossref | GoogleScholarGoogle Scholar |

[14]  A Ray Chowdhuri, D Bhattacharya, SK Sahu, Magnetic nanoscale metal organic frameworks for potential targeted anticancer drug delivery, imaging and as an MRI contrast agent. Dalton Trans 2016, 45, 2963.
         | Magnetic nanoscale metal organic frameworks for potential targeted anticancer drug delivery, imaging and as an MRI contrast agent.Crossref | GoogleScholarGoogle Scholar |

[15]  N Annabi, A Tamayol, JA Uquillas, M Akbari, LE Bertassoni, C Cha, G Camci-Unal, MR Dokmeci, NA Peppas, A Khademhosseini, 25th Anniversary Article: Rational design and applications of hydrogels in regenerative medicine. Adv Mater 2014, 26, 85.
         | 25th Anniversary Article: Rational design and applications of hydrogels in regenerative medicine.Crossref | GoogleScholarGoogle Scholar |

[16]  S Campbell, D Maitland, T Hoare, Enhanced pulsatile drug release from injectable magnetic hydrogels with embedded thermosensitive microgels. ACS Macro Lett 2015, 4, 312.
         | Enhanced pulsatile drug release from injectable magnetic hydrogels with embedded thermosensitive microgels.Crossref | GoogleScholarGoogle Scholar |

[17]  MT Pelegrino, B de Araujo Lima, MHM do Nascimento, CB Lombello, M Brocchi, AB Seabra, Biocompatible and antibacterial nitric oxide-releasing pluronic F-127/chitosan hydrogel for topical applications. Polymers 2018, 10, 452.
         | Biocompatible and antibacterial nitric oxide-releasing pluronic F-127/chitosan hydrogel for topical applications.Crossref | GoogleScholarGoogle Scholar |

[18]  Q Hu, J Yu, M Liu, A Liu, Z Dou, Y Yang, A low cytotoxic cationic metal–organic framework carrier for controllable drug release. J Med Chem 2014, 57, 5679.
         | A low cytotoxic cationic metal–organic framework carrier for controllable drug release.Crossref | GoogleScholarGoogle Scholar |

[19]  R Ananthoji, JF Eubank, F Nouar, H Mouttaki, M Eddaoudi, JP Harmon, Symbiosis of zeolite-like metal–organic frameworks (rho-ZMOF) and hydrogels: Composites for controlled drug release. J Mater Chem 2011, 21, 9587.
         | Symbiosis of zeolite-like metal–organic frameworks (rho-ZMOF) and hydrogels: Composites for controlled drug release.Crossref | GoogleScholarGoogle Scholar |

[20]  Y Liu, Y Xi, J Zhao, J Zhao, J Li, G Huang, J Li, F Fang, L Gu, S Wang, Preparation of therapeutic-laden konjac hydrogel for tumor combination therap. Chem Eng J 2019, 375, 122048.
         | Preparation of therapeutic-laden konjac hydrogel for tumor combination therap.Crossref | GoogleScholarGoogle Scholar |

[21]  S Javanbakht, A Hemmati, H Namazi, A Heydari, Carboxymethylcellulose-coated 5-fluorouracil @MOF-5 nano-hybrid as a bio-nanocomposite carrier for the anticancer oral delivery. Int J Biol Macromol 2020, 155, 876.
         | Carboxymethylcellulose-coated 5-fluorouracil @MOF-5 nano-hybrid as a bio-nanocomposite carrier for the anticancer oral delivery.Crossref | GoogleScholarGoogle Scholar |

[22]  B Chen, Z Yang, Y Zhu, Y Xia, Zeolitic imidazolate framework materials: recent progress in synthesis and applications. J Mater Chem A 2014, 2, 16811.
         | Zeolitic imidazolate framework materials: recent progress in synthesis and applications.Crossref | GoogleScholarGoogle Scholar |

[23]  H Zhang, Q Li, R Liu, X Zhang, Z Li, Y Luan, A versatile prodrug strategy to in situ encapsulate drugs in MOF nanocarriers: a case of cytarabine-IR820 prodrug encapsulated ZIF-8 toward chemo-photothermal therapy. Adv Funct Mater 2018, 28, 1802830.
         | A versatile prodrug strategy to in situ encapsulate drugs in MOF nanocarriers: a case of cytarabine-IR820 prodrug encapsulated ZIF-8 toward chemo-photothermal therapy.Crossref | GoogleScholarGoogle Scholar |

[24]  G Chen, B Yu, C Lu, H Zhang, Y Shen, H Cong, Controlled synthesis of Fe3O4@ZIF-8 nanoparticles for drug delivery. CrystEngComm 2018, 20, 7486.
         | Controlled synthesis of Fe3O4@ZIF-8 nanoparticles for drug delivery.Crossref | GoogleScholarGoogle Scholar |

[25]  NL Torad, M Hu, Y Kamachi, K Takai, M Imura, M Naito, Y Yamauchi, Facile synthesis of nanoporous carbons with controlled particle sizes by direct carbonization of monodispersed ZIF-8 crystals. Chem Commun 2013, 49, 2521.
         | Facile synthesis of nanoporous carbons with controlled particle sizes by direct carbonization of monodispersed ZIF-8 crystals.Crossref | GoogleScholarGoogle Scholar |

[26]  J Zheng, C Cheng, W-J Fang, C Chen, R-W Yan, H-X Huai, C-C Wang, Surfactant-free synthesis of a Fe3O4@ZIF-8 core–shell heterostructure for adsorption of methylene blue. CrystEngComm 2014, 16, 3960.
         | Surfactant-free synthesis of a Fe3O4@ZIF-8 core–shell heterostructure for adsorption of methylene blue.Crossref | GoogleScholarGoogle Scholar |

[27]  H Alijani, A Noori, N Faridi, SZ Bathaie, MF Mousavi, Aptamer-functionalized Fe3O4@MOF nanocarrier for targeted drug delivery and fluorescence imaging of the triple-negative MDA-MB-231 breast cancer cells. J Solid State Chem 2020, 292, 121680.
         | Aptamer-functionalized Fe3O4@MOF nanocarrier for targeted drug delivery and fluorescence imaging of the triple-negative MDA-MB-231 breast cancer cells.Crossref | GoogleScholarGoogle Scholar |

[28]  Y Zhang, Y Yang, J Shi, L Wang, A multimodal strategy of Fe3O4@ZIF-8/GOx@ MnO2 hybrid nanozyme via TME modulation for tumor therapy. Nanoscale 2021, 13, 16571.
         | A multimodal strategy of Fe3O4@ZIF-8/GOx@ MnO2 hybrid nanozyme via TME modulation for tumor therapy.Crossref | GoogleScholarGoogle Scholar |

[29]  C-W Tsai, EHG Langner, The effect of synthesis temperature on the particle size of nano-ZIF-8. Microporous Mesoporous Mater 2016, 221, 8.
         | The effect of synthesis temperature on the particle size of nano-ZIF-8.Crossref | GoogleScholarGoogle Scholar |

[30]  Q Song, SK Nataraj, MV Roussenova, JC Tan, DJ Hughes, W Li, P Bourgoin, MA Alam, AK Cheetham, SA Al-Muhtaseb, E Sivaniah, Zeolitic imidazolate framework (ZIF-8) based polymer nanocomposite membranes for gas separation. Energy Environ Sci 2012, 5, 8359.
         | Zeolitic imidazolate framework (ZIF-8) based polymer nanocomposite membranes for gas separation.Crossref | GoogleScholarGoogle Scholar |

[31]  PC Tan, BS Ooi, AL Ahmad, SC Low, Size control and stability study of zeolitic imidazolate framework-8 to prepare mixed matrix membrane. J Phys Sci 2017, 28, 215.
         | Size control and stability study of zeolitic imidazolate framework-8 to prepare mixed matrix membrane.Crossref | GoogleScholarGoogle Scholar |

[32]  F Pang, M He, J Ge, Controlled synthesis of Fe3O4/ZIF-8 nanoparticles for magnetically separable nanocatalysts. Chem Eur J 2015, 21, 6879.
         | Controlled synthesis of Fe3O4/ZIF-8 nanoparticles for magnetically separable nanocatalysts.Crossref | GoogleScholarGoogle Scholar |

[33]  M He, J Yao, Q Liu, K Wang, F Chen, H Wang, Facile synthesis of zeolitic imidazolate framework-8 from a concentrated aqueous solution. Microporous Mesoporous Mater 2014, 184, 55.
         | Facile synthesis of zeolitic imidazolate framework-8 from a concentrated aqueous solution.Crossref | GoogleScholarGoogle Scholar |

[34]  H Kaur, GC Mohanta, V Gupta, D Kukkar, S Tyagi, Synthesis and characterization of ZIF-8 nanoparticles for controlled release of 6-mercaptopurine drug. J Drug Deliv Sci Technol 2017, 41, 106.
         | Synthesis and characterization of ZIF-8 nanoparticles for controlled release of 6-mercaptopurine drug.Crossref | GoogleScholarGoogle Scholar |

[35]  P Chen, M He, B Chen, B Hu, Size- and dose-dependent cytotoxicity of ZIF-8 based on single cell analysis. Ecotoxicol Environ Saf 2020, 205, 111110.
         | Size- and dose-dependent cytotoxicity of ZIF-8 based on single cell analysis.Crossref | GoogleScholarGoogle Scholar |

[36]  AA Shefa, T Sultana, MK Park, SY Lee, J-G Gwon, B-T Lee, Curcumin incorporation into an oxidized cellulose nanofiber-polyvinyl alcohol hydrogel system promotes wound healing. Mater Des 2020, 186, 108313.
         | Curcumin incorporation into an oxidized cellulose nanofiber-polyvinyl alcohol hydrogel system promotes wound healing.Crossref | GoogleScholarGoogle Scholar |