Magnetic and pH-responsive nanocarriers with multilayer core–shell architecture for anticancer drug delivery

Abstract

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.

Classification of stimuli–responsive polymers as anticancer drug delivery systems

“…Nano-carriers responding to dual-stimuli have also been studied including pH and temperature responsive P(NIPAAm-co-DMAAmco-UA) and P(NIPAAm-co-DMAAm-co-UA)-g-cholesterol NPs loaded with DOX (Soppimath et al, 2005(Soppimath et al, , 2007, paclitoxel-loaded P(NIPAAm-co-AA)-b-PCL NPs (Zhang et al, 2007), mPEG-b-P(HPMA-Lac-co-His), mPEG-b-PLA and cy5.5-PEG-PLA mixed micelles carrying DOX (Chen et al, 2012), PLA-g-P(NIPAAm-co-MAA) and P(NIPAAmco-DMAAm)-b-PCL/PLA micelles carrying adriamycin (Li et al, 2011). A number of examples of pH and magnetic sensitive drug releasing systems include Fe3O4 nanocarriers coated with peptide mimic polymers loaded with DOXÁHCI (Barick et al, 2012) DOX-tethered Fe3O4 conjugates and mPEG-b-PMAA-b-PGMA-Fe3O4 NPs conjugated with adriamycin (Guo et al, 2008).…”

“…Examples of studied temperature and magnetic-responsive systems include Pluronic-Fe3O4 NPs loaded with doxorubicin (Guo et al, 2008).…”

Multifunctional Magnetic Hybrid Nanoparticles as a Nanomedical Platform for Cancer-Targeted Imaging and Therapy

“…The protonation of doxorubicin under acidic conditions increased its water-solubility and induced its release. Recently, our group reported a MFMNP platform that can load drugs with ionizable groups and hydrophobic moieties by the combined action of ionic bonding and hydrophobic interactions (Guo et al, 2008(Guo et al, , 2010 (Fig. 5).…”

“…5. Schematic illustration of the MFMNP structure, and the load and release of model drug adriamycin (ADR) (Guo et al, 2008).…”

Facile synthesis of gold core–polymer shell responsive particles

“…Responsive core-shell nanoparticles have been regularly studied for their potential uses in drug delivery [1][2][3], emulsification and interfacial stabilisation [4][5][6], interfacial transport [7,8] and environmental sensor technologies [9][10][11]. Their properties can also be manipulated to provide functionality when used as building blocks of larger structures such as microcapsules [12] and membranes [13,14].…”