Journal of Polymer Research

, 25:37 | Cite as

pH-responsive magnetic nanocomposites based on poly(2-succinyloxyethyl methacrylate-co-methylmethacrylate) for anticancer doxorubicin delivery applications

  • Aliyeh Ghamkhari
  • Samira Agbolaghi
  • Nahid Poorgholy
  • Bakhshali Massoumi


A novel pH-responsive Fe3O4/poly(2-succinyloxyethylmethacrylate-co-methylmethacrylate) (poly(SEMA-co-MMA)) nanocomposite was designed for anticancer drug delivery applications. For this propose, poly(2-hydroxyethyl methacrylate-co-methylmethacrylate) (poly(HEMA-co-MMA)) was synthesized via reversible addition-fragmentation transfer (RAFT) method. Then, poly(SEMA-co-MMA) was prepared by the esterification of poly(HEMA-co-MMA) copolymer through the reaction with an excess amount of succinic anhydride. The synthesized copolymers with acidic functional groups were adsorbed onto the surface of Fe3O4 nanoparticles and Fe3O4/poly(SEMA-co-MMA) nanocomposite was developed. The pH-sensitivity of Fe3O4/poly(SEMA-co-MMA) nanocomposite was confirmed via dynamic light scattering (DLS) measurements. The Doxorubicin (DOX) encapsulation efficiency was 92.6%. The release rates at pHs of 5.4 and 4 (37 °C) reached 55.7 and 62.4 wt%, respectively, and at pH = 7.4, it possessed a minimum amount around 38.3 wt% after 15 days. The synthesized nanocomposite may be find the drug delivery applications, in part thanks to their smart physicochemical properties.


RAFT Magnetic nanocomposite Drug delivery pH-responsive 



We express our gratitude to the Payame Noor University for supporting this project.


This study was not funded.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Bhowmick A, Saha A, Pramanik N, Banerjee S, Das M, Kundu PP (2015) Novel magnetic antimicrobial nanocomposites forbone tissue engineering applications. RSC Adv 5:25437–25445CrossRefGoogle Scholar
  2. 2.
    Massoumi B, Mousavi-Hamamlu SV, Ghamkhari A, Jaymand M (2017) A novel strategy for synthesis of polystyrene/Fe3O4 nanocomposite: RAFT polymerization, functionalization, and coordination techniques. Polym-Plast Technol Eng 56:873–882CrossRefGoogle Scholar
  3. 3.
    Zhu L, Wang D, Wei X, Zhu X, Li J, Tu C, Su Y, Wu J, Zhu B, Yan D (2013) Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging. J Control Release 169:228–238CrossRefGoogle Scholar
  4. 4.
    Wang W, Zhang Z (2007) Hydrothermal synthesis and characterization of carbohydrate microspheres coated with magnetic nanoparticles. J Dispers Sci Technol 28:557–561CrossRefGoogle Scholar
  5. 5.
    Cheng R, Meng F, Deng C, Klok H-A, Zhong Z (2013) Dual and multi-stimuli responsive polymeric nanoparticles for programmedsite-specific drug delivery. Biomaterials 34:3647–3657CrossRefGoogle Scholar
  6. 6.
    Hergt R, Dutz S, Muller R, Zeisberger M (2006) Magnetic particle hyperthermia: nanoparticle magnetism and materials development for cancertherapy. J Phys Condens Matter 18:S2919–S2934CrossRefGoogle Scholar
  7. 7.
    Karumanchi RS, Doddamane SN, Sampangi C, Todd PW (2002) Field-assisted extraction of cells, particles and macromolecules. Trends Biotechnol 20:72–78CrossRefGoogle Scholar
  8. 8.
    Jiang Y, Guo C, Xia H, Mahmood I, Liu C, Liu H (2009) Magnetic nanoparticles supported ionic liquids for lipase immobilization: Enzyme activity in catalyzing esterification. J Mol Catal B Enzym 58:103–109CrossRefGoogle Scholar
  9. 9.
    Caoa J, Wanga Y, Yu J, Xiaa J, Zhanga C, Yina D, Hafeli UO (2004) Preparation and radiolabeling of surface-modifiedmagnetic nanoparticles with rhenium-188 formagnetic targeted radiotherapy. J Magn Magn Mater 277:165–174CrossRefGoogle Scholar
  10. 10.
    Zhang X, Yang P, Dai Y, Ma P, Li X, Cheng Z, Hou Z, Kang X, Li C, Lin J (2013) Multifunctional up-converting nanocomposites with smart polymer brushes gated mesopores for cell imaging and thermo/pH dual-responsive drug controlled release. Adv Funct Mater 23:4067–4078CrossRefGoogle Scholar
  11. 11.
    Oha JK, Park JM (2011) Iron oxide-based superparamagnetic polymeric nanomaterials: design, preparation, and biomedical application. Prog Polym Sci 36:168–189CrossRefGoogle Scholar
  12. 12.
    Sivudu KS, Rhee KY (2009) Preparation and characterization of pH-responsive hydrogel magnetite nanocomposite. Colloids Surf A Physicochem Eng Asp 349:29–34CrossRefGoogle Scholar
  13. 13.
    Lee JE, Lee DJ, Lee N, Kim B, Choi SH, Hyeon T (2011) Multifunctional mesoporous silica nanocomposite nanoparticles for pH controlled drug release and dual modal imaging. J Mater Chem 21:16869–16872CrossRefGoogle Scholar
  14. 14.
    Poorgholy N, Massoumi B, Jaymand M (2017) A novel starch-based stimuli-responsive nanosystem for theranostic applications. Int J Biol Macromol 97:654–661CrossRefGoogle Scholar
  15. 15.
    Pietsch C, Hoogenboom R, Schubert US (2010) PMMA based soluble polymeric temperature sensors based on UCST transition and solvatochromic dyes. Polym Chem 1:1005–1008CrossRefGoogle Scholar
  16. 16.
    Chi W, Liu S, Yang J, Wang R, Ren H, Zhou H, Chenb J, Guo T (2014) Evaluation of the effects of amphiphilic oligomers in PEI based ternary complexes on the improvement of pDNA delivery. J Mater Chem B 2:5387–5396CrossRefGoogle Scholar
  17. 17.
    Fran J, Lutz C (2006) Solution self-assembly of tailor-made macromolecular building blocks prepared by controlled radical polymerization techniques. Polym Int 55:979–993CrossRefGoogle Scholar
  18. 18.
    Delaittre G, Save M, Gaborieau M, Castignolles P, Rieger J, Charleux B (2012) Synthesis by nitroxide-mediated aqueous dispersion polymerization, characterization, and physical core-crosslinking of pH- and thermoresponsive dynamic diblock copolymer micelles. Polym Chem 3:1526–1538CrossRefGoogle Scholar
  19. 19.
    Beers KL, Boo S, Gaynor SG, Matyjaszewski K (1999) Atom transfer radical polymerization of 2-hydroxyethyl methacrylate. Macromolecules 32:5772–5776CrossRefGoogle Scholar
  20. 20.
    Ahmed M, Narain R (2013) Progress of RAFT based polymers in gene delivery. Prog Polym Sci 38:767–790CrossRefGoogle Scholar
  21. 21.
    Davaran S, Ghamkhari A, Alizadeh E, Massoumi B, Jaymand M (2017) Novel dual stimuli-responsive ABC triblock copolymer: RAFT synthesis, Schizophrenic” micellization and its performance as an anticancer drug delivery nanosystem J Colloid Interface Sci 488:282–293Google Scholar
  22. 22.
    Yang C, Guo W, Cui L, An N, Zhang T, Lin H, Qu F (2014) pH-Responsive magnetic core-shell nanocomposites for drug delivery. Langmuir 30:9819–9827CrossRefGoogle Scholar
  23. 23.
    Bastakoti BP, Guragain S, Nakashima K, Yamauchi Y (2015) Stimuli-induced core–corona inversion of micelle of poly(acrylic acid)-block-poly(N-isopropylacrylamide) and its application in drug delivery. Macromol Chem Phys 216:287–291CrossRefGoogle Scholar
  24. 24.
    Huang G, Zhang K-L, Chen S, Li S-H, Wang L-L, Wang L-P, Liu R, Gao J, Yang H-H (2017) Manganese-iron layered double hydroxide: a theranosticnanoplatform with pH-responsive MRI contrast enhancement and drug release. J Mater Chem B 5:3629–3633CrossRefGoogle Scholar
  25. 25.
    Ghamkhari A, Massoumi B, Jaymand M (2017) Novel ‘schizophrenic’ diblock copolymer synthesized via RAFT polymerization: Poly(2-succinyloxyethyl methacrylate)-b-poly[(N-4-vinylbenzyl),N,N-diethylamine]. Des Monomers Polym 20:190–200CrossRefGoogle Scholar
  26. 26.
    Ma WF, Wu KY, Tang J, Li D, Wei C, Guo J, Wang SL, Wang CC (2012) Magnetic drug carrier with a smart pH-responsive polymer network shell for controlled delivery of doxorubicin. J Mater Chem 22:15206–15214CrossRefGoogle Scholar
  27. 27.
    Li PY, Lai PS, Hung WC, Syu WJ (2010) Poly(L-lactide)-vitamin E TPGS nanoparticles enhanced the cytotoxicity of doxorubicin in drug-resistant MCF-7 breast cancer cells. Biomacromolecules 11:2576–2582CrossRefGoogle Scholar
  28. 28.
    Massoumi B, Ghamkhari A, Agbolaghi S (2017) Dual stimuli-responsive poly(succinyloxyethylmethacrylate-b-N-Isopropylacrylamide) block copolymers as nano-carriers and respective application in Doxorubicin delivery. Int J Polym Mater.
  29. 29.
    Salehi R, Rasouli S, Hamishehkar H (2015) Smart thermo/pH responsive magnetic nanogels for the simultaneous delivery of doxorubicin and methotrexate. Int J Pharm 487:274–284CrossRefGoogle Scholar
  30. 30.
    Bol’bukha YN, Tertykha VA, Yurkovb GY, Ovchenkov EA (2011) Synthesis and properties of nanocomposites based on magnetite and biocompatible polymers. Russ J Appl Chem 84:847–853CrossRefGoogle Scholar
  31. 31.
    Rahimi M, Shojaei S, Safa KD, Ghasemi Z, Salehi R, Yousefi B, Shafiei-Irannejad V (2017) Biocompatible magnetic tris(2-aminoethyl)amine functionalized nanocrystalline cellulose as a novel nanocarrier for anticancer drug delivery of methotrexate. New J Chem 41:2160–2168CrossRefGoogle Scholar
  32. 32.
    Massoumi B, Poorgholy N, Jaymand M (2017) Multi-stimuli responsive polymeric nanosystems for theranostic applications. Int J Polym Mater 66:38–47CrossRefGoogle Scholar
  33. 33.
    Shivakumar HG, Fathima SJ, Radha V, Khanum F (2016) pH and thermosensitive 5-fluorouracil loaded poly (NIPAM-co-AAc) nanogels for cancer therapy. RSC Adv 6:105495–105507CrossRefGoogle Scholar
  34. 34.
    Bawa P, Pillay V, Choonara YE, du Toit LC (2009) Stimuli-responsive polymers and theirapplications in drug delivery. Biomed Mater 4:022001CrossRefGoogle Scholar
  35. 35.
    Cheng R, Wang X, Chen W, Meng F, Deng C, Liuband H, Zhong Z (2012) Biodegradable poly(3-caprolactone)-g-poly(2-hydroxyethyl methacrylate)graft copolymer micelles as superior nano-carriers for “smart” doxorubicinrelease. J Mater Chem 22:11730–11738CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Aliyeh Ghamkhari
    • 1
  • Samira Agbolaghi
    • 2
  • Nahid Poorgholy
    • 1
  • Bakhshali Massoumi
    • 1
  1. 1.Department of ChemistryPayame Noor UniversityTehranIran
  2. 2.Chemical Engineering Department, Faculty of EngineeringAzarbaijan Shahid Madani UniversityTabrizIran

Personalised recommendations