Poly[N-(2-hydroxypropyl)methacrylamide]-Modified Magnetic γ-F2 O3 Nanoparticles Conjugated with Doxorubicin for Glioblastoma Treatment

ChemMedChem. 2020 Jan 7;15(1):96-104. doi: 10.1002/cmdc.201900564. Epub 2019 Nov 12.

Abstract

With the aim to develop a new anticancer agent, we prepared poly[N-(2-hydroxypropyl)methacrylamide-co-methyl 2-methacrylamidoacetate] [P(HP-MMAA)], which was reacted with hydrazine to poly[N-(2-hydroxypropyl)methacrylamide-co-N-(2-hydrazinyl-2-oxoethyl)methacrylamide] [P(HP-MAH)] to conjugate doxorubicin (Dox) via hydrazone bond. The resulting P(HP-MAH)-Dox conjugate was used as a coating of magnetic γ-Fe2 O3 nanoparticles obtained by the coprecipitation method. In vitro toxicity of various concentrations of Dox, P(HP-MAH)-Dox, and γ-Fe2 O3 @P(HP-MAH)-Dox nanoparticles was determined on somatic healthy cells (human bone marrow stromal cells hMSC), human glioblastoma line (GaMG), and primary human glioblastoma (GBM) cells isolated from GBM patients both at a short and prolonged exposition time (up to 7 days). Due to hydrolysis of the hydrazone bond in acid milieu of tumor cells and Dox release, the γ-Fe2 O3 @P(HP-MAH)-Dox nanoparticles significantly decreased the GaMG and GBM cell growth compared to free Dox and P(HP-MAH)-Dox in low concentration (10 nM), whereas in hMSCs it remained without effect. γ-F2 O3 @PHP nanoparticles alone did not affect the viability of any of the tested cells.

Keywords: N-(2-hydroxypropyl)methacrylamide; cancer treatment; doxorubicin; iron oxide; magnetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemistry
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / drug effects
  • Doxorubicin / chemistry*
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry
  • Drug Liberation
  • Ferric Compounds / chemistry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / pathology
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Polymers / chemistry*

Substances

  • Acrylamides
  • Antineoplastic Agents
  • Drug Carriers
  • Ferric Compounds
  • Magnetite Nanoparticles
  • Polymers
  • ferric oxide
  • Doxorubicin
  • N-(2-hydroxypropyl)methacrylamide