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

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.