Water-soluble dendritic-linear triblock copolymer-modified magnetic nanoparticles: preparation, characterization and drug release properties

Abstract

One route has been employed to prepare dendritic-linear block copolymer modified superparamagnetic iron oxide nanoparticles (SPIONs), which consist of a Fe₃O₄ magnetic nanoparticle core and a dendritic-linear block copolymer, the focal point polyamidoamine-type dendron-b-poly(2-dimethylaminoethyl methacrylate)-b-poly(N-isopropylacrylamide) (PAMAM-b-PDMAEMA-b-PNIPAM) shell by two-step atom transfer radical polymerization (ATRP). Firstly, Fe₃O₄ nanoparticles were prepared by a high-temperature solution phase reaction in the presence of iron(III) acetylacetonate [Fe(acac)₃], oleic acid and oleylamine. Then propargyl focal point PAMAM-type dendron (generation 2.0, denoted as propargyl-D_2.0) with four carboxyl acid end groups as a cap displaced the oleic acid and oleylamine on the surfaces. Subsequently, an initiator for ATRP was introduced onto the propargyl-D_2.0-modified Fe₃O₄ nanoparticle surfaces via click chemistry with 2′-azidoethyl-2-bromoisobutylate (AEBIB). PDMAEMA and PNIPAM were grown gradually from nanoparticle surfaces using two-step copper-mediated ATRP. Finally, a crosslinking reaction between PDMAEMA block with 1,2-bis(2-iodoethoxy)ethane (BIEE) was used to stabilize the nanoparticles and reverse aggregation. The modified nanoparticles were subjected to detailed characterization using FT-IR, DLS, XRD and TGA. Magnetization measurements confirmed the characteristic superparamagnetic behavior of all magnetic nanoparticles under room temperature. In addition, doxorubicin (DOX) as an anticancer drug model was loaded into the dendritic-linear block copolymer shell of the modified nanoparticles, and subsequently the drug release was performed in phosphoric acid buffer solution (pH 7.4) at 25 °C or 37 °C. The results verify that dendritic-linear block copolymer-modified nanoparticles as a drug carrier possess thermosensitive drug release behaviors. Furthermore, a methyl tetrazolium (MTT) assay of DOX-loaded dendritic-linear block copolymer-modified nanoparticles against Hela cells was evaluated. The results show that the modified nanoparticles can be used for drug delivery.