Magnetic drug carrier with a smart pH-responsive polymer network shell for controlled delivery of doxorubicin

A smart magnetic targeting drug carrier (MCNC/PAA) comprising an approximately 100 nm sized magnetic colloid nanocrystal cluster (MCNC) core and a pH-responsive cross-linked poly(acrylic acid) (PAA) shell is reported. The abundant carboxyl groups in the shell enable the resultant MCNC/PAA to easily load a large amount of doxorubicin (DOX) (up to 44.6%) via the strong interaction between the DOX and the carboxyl group in a neutral solution. Interestingly, a synergistic pH-responsive effect derived from the entrapped DOX and PAA network was found to effectively manipulate the drug releasing behavior at 37 degrees C. It was found that the premature release was highly restricted at a pH of 7.4, and upon reduction in pH from 7.4 to 5.0 or 4.0, a large amount of drug was rapidly released. Compared with the synthesized MCNC/PNIPAM, MCNC/PHEMA and MCNC/PDMAPMA nanocarriers, the MCNC/PAA was preferably suited to drug delivery. In addition, the composite nanocarriers could be tracked by magnetic resonance imaging (MRI). The cytotoxicity assay of MCNC/PAA to normal cells indicated that the composite nanospheres were biocompatible and suitable as drug carriers. Meanwhile, the DOX-loaded composite nanospheres had more potent cytotoxicity than free DOX to HeLa cells. These results clearly imply that the MCNC/PAA nanocarrier is a promising platform that can be applied to construct a smart drug delivery system with magnetic targeting and pH-stimulation, as well as tracking by MRI.