A new style for synthesis of thermo-responsive Fe3O4/poly (methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) magnetic composite nanosphere and theranostic applications

J Biomater Sci Polym Ed. 2017 Dec;28(17):1985-2005. doi: 10.1080/09205063.2017.1364459. Epub 2017 Aug 18.

Abstract

In this work, a novel thermo-responsive Fe3O4/poly(methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) magnetic composite nanosphere was synthesized for anticancer drug delivery applications. For this propose, the poly(methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) [poly (MMA-b-NIPAAm-b-AAc)] was synthesized via reversible addition-fragmentation transfer method. The physic-chemical characterization of the Fe3O4/poly(MMA-b-NIPAAm-b-AAc) magnetic composite nanosphere was investigated by FTIR, HNMR spectroscopies and GPC, FESEM, XRD, VSM and DLS. The thermo-sensitivity of the Fe3O4/P(MMA-b-NIPAAm-b-AAc) magnetic composite nanosphere was confirmed via DLS at 40 °C. DOX encapsulation efficiency was calculated to be 98.2%. The effect of temperature and pH on release behaviors of stimuli responsive DOX-loaded Fe3O4/P(MMA-b-NIPAAm-b-AAc)] magnetic composite nanosphere were investigated. The release rate at pH 7.4, 5.4 and 4 (T = 37 °C) was reached about 24.4, 42.4 and 57.5 wt%, after 4-5 day. The release rate improved at tumor simulated environment (t:40 °C and pH ≤ 5.4). The cytotoxic effects of the magnetic composite nanosphere were appraised by MTT assay and the results indicated that novel developed smart nanocomposite here was nontoxic to MCF-7 cells and can be applied as anti-cancer drug delivery system. Also, the results of the Cellular uptake of MCF7 cells treated with rhodamine labeled DOX-loaded nanocarrier for 2 h have indicated that DOX can be applied as cytotoxic agent and targeting ligand.

Keywords: RAFT; drug delivery; magnetic composite nanosphere; stimuli responsive polymer; tumor targeting.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry
  • Ferrosoferric Oxide / chemical synthesis
  • Ferrosoferric Oxide / chemistry
  • Humans
  • MCF-7 Cells
  • Metal Nanoparticles / chemistry*
  • Nanocomposites
  • Polymethyl Methacrylate / chemical synthesis
  • Polymethyl Methacrylate / chemistry
  • Theranostic Nanomedicine

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Doxorubicin
  • Polymethyl Methacrylate
  • Ferrosoferric Oxide