RGDS- and doxorubicin-modified poly[N-(2-hydroxypropyl)methacrylamide]-coated γ-Fe2O3 nanoparticles for treatment of glioblastoma
Horák D., Turnovcová K., Plichta Z., Mareková D., Proks V., Kaiser R., Netuka D., Jendelová P.
Abstract: Block copolymer comprising of hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHP) and reactive poly[N-(2-hydrazinyl-2-oxoethyl)methacrylamide] (PMAH) was synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization and conjugated with doxorubicin (Dox) and/or RGDS targeting peptide via one-step reaction using N-γ-maleimidobutyryl-oxysuccinimide ester. The resulting copolymer served as a coating of magnetic γ-Fe2O3 nanoparticles that were tested in cell proliferation and in vivo experiments on a mice model with inoculated rat C6 glioblastoma tumor. The nanoparticles conjugated with RGDS peptide and doxorubicin easily engulfed both C6 tumor cell line, primary glioblastoma (GB) cells, and human mesenchymal stem cells (hMSC) used as a control; the particles decreased the GB cell growth by 45% compared to control cells without any treatment. Moreover, the γ-Fe2O3@P(HP-MAH)-RGDS-Dox nanoparticles injected into C6 glioblastoma cell-derived tumors grown in the posterior flank of mice decreased the tumor size and more apoptotic cells were spread compared to that treated with free Dox. Graphical Abstract: [InlineMediaObject not available: see fulltext.]