Poly[ N ‐(2‐hydroxypropyl)methacrylamide]‐Modified Magnetic γ‐F 2 O 3 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‐Fe 2 O 3 nanoparticles obtained by the coprecipitation method. In vitro toxicity of various concentrations of Dox, P(HP‐MAH)‐Dox, and γ‐Fe 2 O 3 @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‐Fe 2 O 3 @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‐F 2 O 3 @PHP nanoparticles alone did not affect the viability of any of the tested cells.