| Affiliation: | 1. Department of Polymer Particles, Institute of Macromolecular Chemistry CAS, Heyrovského nám. 2, 162 06 Prague 6, Czech Republic;2. Department of Neuroregeneration, Institute of Experimental Medicine CAS, Vídeňská 1083, 142 20 Prague 4, Czech Republic
2nd Faculty of Medicine, Charles University, V úvalu 84, 150 06 Prague 5, Czech Republic;3. Department of Neuroregeneration, Institute of Experimental Medicine CAS, Vídeňská 1083, 142 20 Prague 4, Czech Republic;4. Department of Neurosurgery and Neurooncology, First Faculty of Medicine and Military University Hospital, U Vojenské nemocnice 1200, 169 02 Prague 6, Czech Republic |
| Abstract: | With the aim to develop a new anticancer agent, we prepared polyN-(2-hydroxypropyl)methacrylamide-co-methyl 2-methacrylamidoacetate] P(HP-MMAA)], which was reacted with hydrazine to polyN-(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-Fe2O3 nanoparticles obtained by the coprecipitation method. In vitro toxicity of various concentrations of Dox, P(HP-MAH)-Dox, and γ-Fe2O3@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-Fe2O3@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-F2O3@PHP nanoparticles alone did not affect the viability of any of the tested cells. |
