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pH- and thermoresponsive aggregation behavior of polymer-grafted magnetic nanoparticles

Polymer Journal volume 53, pages 1011–1018 (2021)Cite this article

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Abstract

Commercially available Resovist is a superparamagnetic iron oxide used as a magnetic resonance imaging contrast agent. In this study, pH- and thermoresponsive poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) was grafted onto the surface of Resovist (PDMA@Rv) via atom transfer radical polymerization. The zeta potential of PDMA@Rv was positive at pH values lower than the acid dissociation constant (pKa = 6.2) of the grafted PDMAEMA because of the protonation of the pendant tertiary amino groups. At pH 5.4, PDMAEMA became hydrophilic, and the size of PDMA@Rv remained constant, irrespective of temperature. Above pH 7, the zeta potential showed a negative value because of the deprotonation of the pendant tertiary amino groups in the grafted PDMAEMA chains. PDMA@Rv formed aggregates and showed lower critical solution temperature behavior above pH 7. The phase transition temperature (Tp), which is defined as the temperature at which the particle size began to increase during the heating process, was 61.5 °C for PDMA@Rv at pH 7.4. PDMA@Rv contained a larger number of core particles of iron oxide than Resovist, which reduced the initial magnetic susceptibility due to the interaction of the core magnetic particles inside PDMA@Rv.

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References

  1. Long NV, Thi CM, Yong Y, Cao Y, Wu H, Nogami M. Synthesis and characterization of fe-based metal and oxide based nanoparticles: discoveries and research highlights of potential applications in biology and medicine. Recent Pat Nanotechnol. 2014;8:52–61.

    Article  CAS  Google Scholar 

  2. Ruiz-Molina D, Novio F, Roscini C. Bio- and bioinspired nanomaterials. Wiley-VCH. 2014:9;229–53.

  3. Dewey W, Hopwood L, Sapareto S, Gerweck L. Cellular responses to combinations of hyperthermia and radiation. Radiology. 1977;123:463–74.

    Article  CAS  Google Scholar 

  4. Saito H, Mitobe K, Minamiya Y. Medical application of magnetic materials for cancer therapy. Drug Deliv Syst. 2014;29:304–14.

    Article  CAS  Google Scholar 

  5. Ito A, Shinkai M, Honda H, Kobayashi T. Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng. 2005;100:1–11.

    Article  CAS  Google Scholar 

  6. Shubayev VI, Pisanic TR, Jin S. Magnetic nanoparticles for theragnostics. Adv Drug Deliv Rev. 2009;61:467–77.

    Article  CAS  Google Scholar 

  7. Tartaj P, del Puerto Morales M, Veintemillas-Verdaguer S, González-Carreño T, Serna CJ. The preparation of magnetic nanoparticles for applications in biomedicine. J Phys D Appl Phys. 2003;36:R182.

    Article  CAS  Google Scholar 

  8. Santhosh B, Ulrih NP. Multifunctional superparamagnetic iron oxide nanoparticles: promising tools in cancer theranostics. Cancer Lett. 2013;336:8–17.

    Article  CAS  Google Scholar 

  9. Huang G, Chen H, Dong Y, Luo X, Yu H, Moore Z, et al. Superparamagnetic iron oxide nanoparticles: amplifying ROS stress to improve anticancer drug efficacy. Theranostics. 2013;3:116–26.

    Article  CAS  Google Scholar 

  10. Singh A, Sahoo SK. Magnetic nanoparticles: a novel platform for cancer theranostics. Drug Disco Today. 2014;19:474–81.

    Article  CAS  Google Scholar 

  11. Chen J, Shi M, Liu P, Ko A, Zhong W, Liao W, et al. Reducible polyamidoamine-magnetic iron oxide self-assembled nanoparticles for doxorubicin delivery. Biomaterials. 2014;35:1240–48.

    Article  CAS  Google Scholar 

  12. Fang C, Kievit FM, Veiseh O, Stephen ZR, Wang T, Lee D, et al. Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach. J Controlled Rel. 2012;162:233–41.

    Article  CAS  Google Scholar 

  13. Karimzadeh I, Aghazadeh M, Ganjali MR, Norouzi P, Shirvani-Arani S, Doroudi T, et al. A novel method for preparation of bare and poly(vinylpyrrolidone) coated superparamagnetic iron oxide nanoparticles for biomedical applications. Mater Lett 2016;179:5–8.

    Article  CAS  Google Scholar 

  14. Liu Y, Feng G, Guo X, Wu Z, Chen Y, Xiang W, et al. Employing MnO as multifunctional polysulfide reservoirs for enhanced-performance Li-S batteries. J Alloy Compd 2018;748:100–10.

    Article  CAS  Google Scholar 

  15. Zhu K, Deng Z, Liu G, Hu J, Liu S. Photoregulated cross-linking of superparamagnetic iron oxide nanoparticle (SPION) loaded hybrid nanovectors with synergistic drug release and magnetic resonance (MR) imaging enhancement. Macromolecules. 2017;50:1113–25.

    Article  CAS  Google Scholar 

  16. Li L, Shang L, Chen K, Wang Q, Luo J, Zhou Q, et al. Redox-sensitive core cross-linked polyethylene glycol-polypeptide hybrid micelles for anticancer drug delivery. J Nanosci Nanotechnol 2017;17:4532–41.

    Article  CAS  Google Scholar 

  17. Yar Y, Khodadust R, Akkoc Y, Utkur M, Saritas EU, Gozuacik D, et al. Development of tailored SPION-PNIPAM nanoparticles by ATRP for dually responsive doxorubicin delivery and MR imaging. J Mater Chem B. 2018;6:289–300.

    Article  CAS  Google Scholar 

  18. Patra S, Roy E, Karfa P, Kumar S, Madhuri R, Sharma PK. Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment. ACS Appl Mater Interfaces. 2015;7:9235–46.

    Article  CAS  Google Scholar 

  19. Li L, Zhang C, Zhang R, Xu Z, Xu Z. Multifunctional magnetized porous silica covered with Poly(2-dimethylaminoethyl methacrylate) for pH controllable drug release and magnetic resonance imaging. ACS Appl Nano Mater. 2018;1:5027–34.

    Article  CAS  Google Scholar 

  20. Majewski AP, Schallon A, Jérôme V, Freitag R, Müller AHE, Schmalz H. Dual-responsive magnetic core–shell nanoparticles for nonviral gene delivery and cell separation. Biomacromolecules. 2012;13:857–66.

    Article  CAS  Google Scholar 

  21. Stark WJ, Stoessel PR, Wohlleben W, Hafner A. Industrial applications of nanoparticles. Chem Soc Rev. 2015;44:5793–805.

    Article  CAS  Google Scholar 

  22. Reimer P, Schuierer G, Balzer T, Peters PE. Application of a superparamagnetic iron oxide (Resovist) for MR imaging of human cerebral blood volume. Magn Reson Med. 1995;34:694–7.

    Article  CAS  Google Scholar 

  23. Reimer P, Balzer T. Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol. 2003;13:1266–76.

    Article  Google Scholar 

  24. Sato I, Umemura M, Mitsudo K, Kioi M, Nakashima H, Iwai T, et al. Hyperthermia generated with ferucarbotran (Resovist®) in an alternating magnetic field enhances cisplatin-induced apoptosis of cultured human oral cancer cells. J Physiol Sci. 2014;64:177–83.

    Article  CAS  Google Scholar 

  25. Ohki A, Tanoue M, Kobayashi S, Murase K. Magnetic particle imaging for quantitative evaluation of tumor response to magnetic hyperthermia treatment combined with chemotherapy using cisplatin. Therm Med. 2017;33:39–51.

    Article  Google Scholar 

  26. Agarwal S, Zhang Y, Maji S, Greiner A. PDMAEMA based gene deliver. Mater Today. 2012;15:388–93.

    Article  CAS  Google Scholar 

  27. Huang SJ, Ke JH, Chen GJ, Wang LF. One-pot synthesis of PDMAEMA-bound iron oxide nanoparticles for magnetofection. J Mater Chem B. 2013;1:5916–24.

    Article  CAS  Google Scholar 

  28. Lam JKW, Ma Y, Armes SP, Lewis AL, Baldwin T, Stolnik SJ. Phosphorylcholine–polycation diblock copolymers as synthetic vectors for gene delivery. J Control Rel. 2004;100:293–312.

    Article  CAS  Google Scholar 

  29. Nagase K, Kobayashi J, Kikuchi A, Akiyama Y, Kanazawa H, Okano T. Effects of graft densities and chain lengths on separation of bioactive compounds by nanolayered thermoresponsive polymer brush surfaces. Langmuir. 2008;24:511–7.

    Article  CAS  Google Scholar 

  30. Liang Y, Liu Z, Dai R, Meng W, Deng Y. Influence of graft density of poly(N-Isopropylacrylamide)-grafted silica on separation performance. Chromatographia. 2015;78:1349–57.

    Article  CAS  Google Scholar 

  31. Butun V, Armes SP, Billingham NC. Synthesis and aqueous solution properties of near-monodisperse tertiary amine methacrylate homopolymers and diblock copolymers. Polymer. 2001;42:5993–6008.

    Article  CAS  Google Scholar 

  32. Arai K, Karikomi M, Kimura T. Preparation and evaluation of poly[2-(dimethylamino) ethyl methacrylate]-carbon black complex. Kobunshi Ronbunsh. 2008;65:695–9.

    Article  Google Scholar 

  33. Han D, Tong X, Boissière O, Zhao Y. General strategy for making CO2-switchable polymers. ACS Macro Lett. 2012;1:57–61.

    Article  CAS  Google Scholar 

  34. Fournier D, Hoogenboom R, Thijs HML, Paulus RM, Schubert US. Tunable pH- and temperature-sensitive copolymer libraries by reversible addition-fragmentation chain transfer copolymerizations of methacrylates. Macromolecules. 2007;40:915–20.

    Article  CAS  Google Scholar 

  35. Lawaczeck R, Bauer H, Frenzel T, Hasegawa M, Ito Y, Kito K, et al. Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical Profile of SH U555A. Acta Radio. 1997;38:584–97.

    CAS  Google Scholar 

  36. Song J, Birbach NL, Hinestroza JP. Deposition of silver nanoparticles on cellulosic fibers via stabilization of carboxymethyl groups. Cellulose. 2012;19:411–24.

    Article  CAS  Google Scholar 

  37. Shi G, Takeda R, Trisnanto SB, Yamada T, Ota S, Takemura Y. Enhanced specific loss power from Resovist achieved by aligning magnetic easy axes of nanoparticles for hyperthermia. J Magn Magn Mater. 2019;473:148–54.

    Article  CAS  Google Scholar 

  38. Achilleos DS, Vamvakaki M. Multiresponsive spiropyran-based copolymers synthesized by atom transfer radical polymerization. Macromolecules. 2010;43:7073–81.

    Article  CAS  Google Scholar 

Download references

Funding

This work was funded by a Grant-in-Aid for Scientific Research (17H03071) from the Japan Society for the Promotion of Science (JSPS), JSPS Bilateral Joint Research Projects (JPJSBP120203509), and the Cooperative Research Program of “Network Joint Research Center for Materials and Devices (20204034)”.

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Authors and Affiliations

  1. Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan

    Shinichiro Kano, Kengo Takagi & Shin-ichi Yusa

  2. Graduate School of Engineering, Yokohama National University, Yokohama, Kanagawa, Japan

    Tsuyoshi Yamaminami & Yasushi Takemura

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  1. Shinichiro Kano
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Correspondence to Shin-ichi Yusa.

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Kano, S., Takagi, K., Yamaminami, T. et al. pH- and thermoresponsive aggregation behavior of polymer-grafted magnetic nanoparticles. Polym J 53, 1011–1018 (2021). https://doi.org/10.1038/s41428-021-00494-y

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