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A multifunctional nanocarrier with multilayer core-shell architecture was prepared by alkaline coprecipitation of ferric and ferrous ions in the presence of a triblock copolymer, methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-block-poly(glycerol monomethacrylate) (denoted MPEG-b-PMAA-b-PGMA), in aqueous solution. The core of the nanocarrier is a superparamagnetic Fe 3 O 4 nanoparticle, on which the PGMA block of the triblock copolymer is attached. The PMAA block forms the inner shell and the MPEG block forms the outermost shell. The anticancer agent adriamycin (ADR), as a model drug with an amine group and a hydrophobic moiety, was loaded into the nanocarrier at pH 7.4 by combined action of ionic bonding and hydrophobic interaction. The hydrophobic main chain of PMAA and the hydrophobic microenvironment created by MPEG contribute to the hydrophobic interaction. The synergistic effect between the ionic bond and the hydrophobic interaction significantly enhances the loading capacity. At endosomal/lysosomal acidic pH (<5.5), protonation of polycarboxylate anions of PMAA (pK a ¼ 5.6) breaks the ionic bond between the carrier and ADR, leading to the release of ADR because the hydrophobic interaction alone is very weak due to the relatively hydrophilic character of the nanocarrier.

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Methoxypoly(ethylene glycol)-oligo(aspartic acid) (MPEG-Asp(n)-NH(2), n = 2-5) hybrid block copolymers were synthesized and used as stabilizers to prepare superparamagnetic Fe(3)O(4) nanoparticles with magnetite as the inner core and and poly(ethylene glycol) as the hydrophilic outer shell. The aqueous dispersions of the nanoparticles were stable at pH 2-11 and in 1M NaCl solution, when repeat number, n, was 3 or more. Transmission electron microscopy showed that the nanoparticles, stabilized with MPEG-Asp(3)-NH(2), were about 14 nm in diameter. Magnetic measurements indicated that MPEG-Asp(3)-NH(2)-coated iron oxide nanoparticles showed superparamagnetic behavior. Cell adhesion assay and in vitro cell viability/cytotoxicity studies showed that MPEG-Asp(3)-NH(2)-coated iron oxide nanoparticles had less effect on cell adhesion/viability and morphology, and less cytotoxicity compared with uncoated, poly (acrylic acid)-coated, and MPEG-poly(acrylic acid)-coated iron oxide nanoparticles.