Construction of small-sized superparamagnetic Janus nanoparticles and their application in cancer combined chemotherapy and magnetic hyperthermia

Abstract

Novel Janus nanoparticles (J-NPs) are developed by using single iron oxide (Fe₃O₄) nanoparticles as the core and hydrophobic/hydrophilic polymeric brushes as the cloak. Because of the superparamagnetism and asymmetric functionality of J-NPs, they are used as drug carriers and therapeutic agents for cancer chemotherapy and magnetic hyperthermia with a magnetic resonance imaging (MRI) guide. The asymmetric functionality is constituted of hydrophobic polymethyl methacrylate (PMMA) brushes and hydrophilic polyacrylic acid (PAA) brushes, which are 'grafting to' or 'grafting from' Fe₃O₄ nanoparticles via activators regenerated by electron transfer atom transfer radical polymerization. The terminal chains of PMMA and PAA brushes are coordinated with Fe₃O₄ nanoparticles, so PMMA/Fe₃O₄/PAA J-NPs possess structural stability in solvents. Because of the brush-structure, PMMA/Fe₃O₄/PAA J-NPs show high encapsulation efficiency (89.75 ± 2.35%) and loading capacity (8.95 ± 0.26%). Under the alternating magnetic field (AMF), drug-loaded J-NPs achieve the highest cell proliferation-inhibition ratio in the cell proliferation test in vitro and the tumor growth inhibition test in vivo compared to single chemotherapy or magnetic hyperthermia. Meanwhile, J-NPs show good T₂ imaging.