Fabrication and evaluation of controlled release of Doxorubicin loaded UiO-66-NH2 metal organic frameworks

Document Type : Original Article


1 Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran

3 Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran Extractive Metallurgy Kinetics of Metallurgical Processes Steel Making SMA Nanostructures Bionanomaterials


The metal-organic frameworks (MOFs) due to their large specific surface area and high biocompatibility are suitable as carriers for drug delivery systems (DDSs). In the present study, doxorubicin (DOX) as an anticancer drug was loaded into the UiO-66-NH2 MOFs to decrease the adverse side effects of pristine DOX use and to increase its efficiency through the controlled release of DOX from MOFs. The MOFs were synthesized via microwave heating method and characterized using X-ray diffraction, scanning electron microscopy, and Brunauer-Emmett- Teller analysis. The drug loading efficiency, drug release profiles from synthesized MOFs and pharmacokinetic studies were investigated. The biocompatibility of drug-loaded-UiO-66-NH2 MOFs was also evaluated by their incubation in L929 normal fibroblast cells. The average particle sizes of UiO-66-NH2 MOFs and DOX loaded-MOFs were found to be 175 nm, and 200 nm respectively. The Brunauer-Emmett- Teller surface area of UiO-66-NH2 MOFs and DOX (100 μg mL-1) loaded-UiO-66-NH2 MOFs were estimated to be 1052 m2g-1, and 121 m2g-1, respectively. The synthesized MOFs exhibited high capability for the controlled release of DOX from MOFs as a pH sensitive carrier. The DOX release data were best described using Korsmeyer-Peppas pharmacokinetic model (R2≥0.985). The cell viability of synthesized MOFs against fibroblast normal cells was found to be higher than 90%. It could be concluded that the UiO-66-NH2 MOFs could be used as an effective pH sensitive carrier for loading anticancer drugs.


  1. Zamboni. W. C, “Liposomal, nanoparticle, and conjugated formulations of anticancer agents”, Clinical Cancer Research, Vol.11, No. 23, (2005), 8230-8234, doi: 10.1158/1078-0432.
  2. Dizaji. B. F, Khoshbakht. S, Farboudi. A, Azarbaijan. M. H, and Irani. M, “Far-reaching advances in the role of carbon nanotubes in cancer therapy”, Life Sciences, Vol. 257, (2020), 118059, doi: 10.1016/j.lfs.2020.118059.
  3. Fathi. M, Alami-Milani. M, Geranmayeh. M. H, Barar. J, Erfan-Niya. H, and Omidi. Y, “Dual thermo-and pH-sensitive injectable hydrogels of chitosan/(poly (N-isopropylacrylamide-co-itaconic acid)) for doxorubicin delivery in breast cancer”, International Journal of Biological Macromolecules, Vol. 128, (2019), 957-964, doi:10.1016/j.ijbiomac.2019.01.122.
  4. Pirouz. F, Najafpour. G, Jahanshahia. M, and Sharifzadeh Baei. M, "Plant-based calcium fructoborate as boron-carrying nanoparticles for neutron cancer therapy", International Journal of Engineering, Transactions A: Basics, Vol. 32, No. 4, (2019), 460-466. doi: 10.5829/ije.2019.32.04a.01.
  5. Ma. B, Zhuang. W, Wang. Y, Luo. R, and Wang. Y, pH-sensitive doxorubicin-conjugated prodrug micelles with charge-conversion for cancer therapy. Acta Biomaterialia, Vol. 70, (2018), 186-196, doi: 10.1016/j.actbio.2018.02.008.
  6. Abasian. P, Radmansouri. M, Jouybari. M. H, Ghasemi. M. V, Mohammadi. A, Irani. M, and Jazi. F. S, Incorporation of magnetic NaX zeolite/DOX into the PLA/chitosan nanofibers for sustained release of doxorubicin against carcinoma cells death in vitro. International Journal of Biological Macromolecules, Vol. 121, (2019), 398-406, doi: 10.1016/j.ijbiomac.2018.09.215.
  7. Rezaei. S, Mohammadi. M, Najafpour. G, D, Moghadamnia. A, Kazemi. S, and Nikzad M, “Separation of curcumin from curcuma longa L. and its conjugation with silica nanoparticles for anti-cancer activities”. International Journal of Engineering, Transactions B: Applications, Vol.31, No. 11, (2018), 1803-1809, doi:10.5829/ije.2018.31.11b.01.
  8. Bagheri. M, Sangpour. P, Badiei. E, and Pazouki. M, Graphene oxide antibacterial sheets: Synthesis and characterization (research note). International Journal of Engineering, Transactions C: Aspects, Vol. 27, No. 12, (2014), 1803-1808, doi: 10.5829/idosi.ije.2014.27.12c.01
  9. Hassanzadeh Nemati. N, and Mirhadi. S. M, “Synthesis and characterization of highly porous TiO2 scaffolds for bone defects”, International Journal of Engineering, Transactions A: Basics, Vol. 33, No. 1, (2020), 134-140, doi: 10.5829/ije.2020.33.01a.15.
  10. Rozilah. A, Jaafar. C. N, Sapuan, S. M, Zainol. I, and Ilyas. R. A, “The effects of silver nanoparticles compositions on the mechanical, physiochemical, antibacterial, and morphology properties of sugar palm starch biocomposites for antibacterial coating”, Polymers, Vol.12, (2020), 2605, doi: 10.3390/polym12112605
  11. Huxford. R. C, Della Rocca. J, and Lin. W, “Metal–organic frameworks as potential drug carriers”, Current Opinion in Chemical Biology, Vol. 14, No. 2, (2010), 262-268, doi: 10.1016/j.cbpa.2009.12.012.
  12. Zheng. H, Zhang. Y, Liu. L, Wan. W, Guo. P, Nyström. A. M, and Zou. X, “One-pot synthesis of metal–organic frameworks with encapsulated target molecules and their applications for controlled drug delivery”, Journal of the American Chemical Society, Vol. 138, No. 3, (2016), 962-968, doi: 10.1021/jacs.5b11720.
  13. Beg. S, Rahman. M, Jain. A, Saini. S, Midoux. P, Pichon. C, and Akhter. S, “Nanoporous metal organic frameworks as hybrid polymer–metal composites for drug delivery and biomedical applications”. Drug Discovery Today, Vol. 22, No. 4, (2017), 625-637, doi: 10.1016/j.drudis.2016.10.001.
  14. Pirzadeh. K, Ghoreyshi. A. A, Rohani. S, and Rahimnejad. M, “Strong Influence of Amine Grafting on MIL-101 (Cr) Metal–Organic Framework with Exceptional CO2/N2 Selectivity”, Industrial & Engineering Chemistry Research, Vol. 59, No. 1, (2019), 366-378, doi: 10.1021/acs.iecr.9b05779.
  15. Wang. L, Zheng. M, Xie. Z, "Nanoscale metal–organic frameworks for drug delivery: a conventional platform with new promise", Journal of Materials Chemistry B., Vol. 6, No. 5, (2018), 707-717, doi: 10.1039/C7TB02970E.
  16. Zheng. C, Wang. Y, Phua. S. Z. F, Lim. W. Q, and Zhao. Y, “ZnO–DOX@ ZIF-8 core–shell nanoparticles for pH-responsive drug delivery”, ACS Biomaterials Science & Engineering, Vol. 3, No. 10, (2017), 2223-2229, doi: 10.1021/acsbiomaterials.7b00435.
  17. Gordon. J, Kazemian. H, and Rohani. S, “MIL-53 (Fe), MIL-101, and SBA-15 porous materials: potential platforms for drug delivery”, Materials Science and Engineering: C, Vol. 47, (2015), 172-179, doi: 10.1016/j.msec.2014.11.046.
  18. Jarai. B. M, Stillman. Z, Attia. L, Decker. G. E, Bloch. E. D, and Fromen, C. A, “Evaluating UiO-66 metal–organic framework nanoparticles as acid-sensitive carriers for pulmonary drug delivery applications. ACS Applied Materials & Interfaces, Vol. 12, No. 35, (2020), 38989-39004, doi: 10.1021/acsami.0c10900.
  19. Nasrabadi. M, Ghasemzadeh. M. A, and Monfared. M. R. Z, “The preparation and characterization of UiO-66 metal–organic frameworks for the delivery of the drug ciprofloxacin and an evaluation of their antibacterial activities”, New Journal of Chemistry, Vol. 43, No. 40, (2019), 16033-16040, doi: 10.1039/C9NJ03216A.
  20. Katz. M. J, Brown. Z. J, Colón. Y. J, Siu. P. W, Scheidt. K. A, Snurr. R. Q, and Farha, O. K. A, “facile synthesis of UiO-66, UiO-67 and their derivatives”,  Chemical Communications, Vol. 49, No. 82, (2013), 9449-9451, doi:10.1039/C3CC46105J.
  21. Gangu. K. K, Maddila. S, Mukkamala. S. B, and Jonnalagadda, S. B. “A review on contemporary metal–organic framework materials”, Inorganica Chimica Acta, Vol. 446, (2016) 61-74, doi: 10.1016/j.ica.2016.02.062.
  22. Jamkhande. P. G, Ghule. N. W, Bamer. A. H, and Kalaskar, M. G, “Metal nanoparticles synthesis: An overview on methods of preparation, advantages and disadvantages, and applications”, Journal of Drug Delivery Science and Technology, Vol. 53, (2019),  101174, doi: 10.1016/j.jddst.2019.101174
  23. Rane. A. V, Kanny. K, Abitha. V. K, and Thomas. S, “Methods for synthesis of nanoparticles and fabrication of nanocomposites”. In Synthesis of inorganic nanomaterials (pp. 121-139)”. (2018).  Woodhead Publishing. doi: 10.1016/B978-0-08-101975-7.00005-1.
  24. Taddei. M, Dau. P. V, Cohen. S. M, Ranocchiari. M, van Bokhoven. J. A, Costantino. F, and Vivani. R, “Efficient microwave assisted synthesis of metal–organic framework UiO-66: optimization and scale up”, Dalton Transactions, Vol. 44, No. 31, (2015), 14019-14026, doi: 10.1039/C5DT01838B.
  25. Choi. J. S, Son. W. J, Kim. J, and Ahn. W. S, “Metal–organic framework MOF-5 prepared by microwave heating: Factors to be considered”,  Microporous and Mesoporous Materials, Vol. 116, No. 1-3, (2008), 727-731, doi: 10.1016/j.micromeso.2008.04.033.
  26. Ni. Z, and Masel. R. I, “Rapid production of metal− organic frameworks via microwave-assisted solvothermal synthesis”, Journal of the American Chemical Society, Vol. 128, No. 38, (2006), 12394-12395, doi: 10.1021/ja0635231.
  27. Pirzadeh. K, Esfandiari. K, Ghoreyshi. A. A, and Rahimnejad, M, “CO2 and N2 adsorption and separation using aminated UiO-66 and Cu3 (BTC) 2: A comparative study”, Korean Journal of Chemical Engineering, Vol. 37, No.3, (2020), 513-524, doi: 0.1007/s11814-019-0433-5.
  28. Pirzadeh. K, Ghoreyshi. A. A, Rahimnejad. M, and Mohammadi. M, “Electrochemical synthesis, characterization and application of a microstructure Cu 3 (BTC) 2 metal organic framework for CO2 and CH4 separation”, Korean Journal of Chemical


















 Engineering, Vol. 35, No. 4, (2018), 974-983, doi: 10.1007/s11814-017-0340-6

  1. Chowdhuri. A. R, Laha. D, Chandra. S, Karmakar. P, and Sahu. S. K, “Synthesis of multifunctional upconversion NMOFs for targeted antitumor drug delivery and imaging in triple negative breast cancer cells”, Chemical Engineering Journal, Vol. 319, (2017), 200-211, doi: 10.1016/j.cej.2017.03.008.
  2. Orellana-Tavra. C, Baxter. E. F, Tian. T, Bennett. T. D, Slater. N. K, Cheetham. A. K, and Fairen-Jimenez. D, “Amorphous metal–organic frameworks for drug delivery”, Chemical Communications, Vol. 51, No. 73, (2015), 13878-13881, doi: 10.1039/C5CC05237H
  3. Jamshidifard. S, Koushkbaghi. S, Hosseini. S, Rezaei. S, Karamipour. A, and Irani. M, “Incorporation of UiO-66-NH2 MOF into the PAN/chitosan nanofibers for adsorption and membrane filtration of Pb (II), Cd (II) and Cr (VI) ions from aqueous solutions”, Journal of Hazardous Materials, Vol. 368, (2019), 10-20, doi: 10.1016/j.jhazmat.2019.01.024.
  4. Farboudi. A, Mahboobnia. K, Chogan. F, Karimi. M, Askari. A, Banihashem. S, and Irani. M, “UiO-66 metal organic framework nanoparticles loaded carboxymethyl chitosan/poly ethylene oxide/polyurethane core-shell nanofibers for controlled release of doxorubicin and folic acid”, International Journal of Biological Macromolecules, Vol. 150, (2020), 178-188, doi: 10.1016/j.ijbiomac.2020.02.067.
  5. Suresh. K, and Matzger. A. J, “Enhanced drug delivery by dissolution of amorphous drug encapsulated in a water unstable metal–organic framework (MOF)”, Angewandte Chemie, Vol. 131, No. 47, (2019), 16946-16950, doi: 10.1002/ange.201907652.
  6. You. J, Li. W, Yu. C, Zhao. C, Jin. L, Zhou. Y, and Wang. O, “Amphiphilically modified chitosan cationic nanoparticles for drug delivery”, Journal of Nanoparticle Research, Vol. 15, No. 12, (2013), 1-10, doi: 10.1007/s11051-013-2123-2.
  7. Guo. S, Qiao. Y, Wang. W, He. H, Deng. L, Xing. J, and Dong. A, “Poly (ε-caprolactone)-graft-poly (2-(N, N-dimethylamino) ethyl methacrylate) nanoparticles: pH dependent thermo-sensitive multifunctional carriers for gene and drug delivery”, Journal of Materials Chemistry, Vol. 20, No. 33 (2010) 6935-6941. DOI: 10.1039/C0JM00506A.
  8. Kamba. S. A, Ismail. M, Hussein-Al-Ali. S. H, Ibrahim. T. A. T, and Zakaria. Z. A. B, “In vitro delivery and controlled release of doxorubicin for targeting osteosarcoma bone cancer”, Molecules, Vol. 18, No. 9, (2013), 10580-10598, doi: 10.3390/molecules180910580.