Dual-pH-sensitivity and tumour targeting core–shell particles for intracellular drug delivery

Abstract

The principal problem in the area of drug delivery is achieving better selectivity and controllability. A new core–shell nanoparticle composite (denoted MSN@Tf@Polymer) with dual-pH-sensitivity has been prepared as a drug carrier for intracellular drug delivery and release. MSN@Tf@Polymer consists of mesoporous silica nanoparticles (MSN), green-transferrin (Tf) and diblock copolymer (poly-2-diisopropylamino ethylmethacrylate-b-methoxy-poly ethyleneglycol: mPEG₄₅-PDPA_n). The core–shell structure is self-assembled layer by layer. Results show that nearly 80% doxorubicin hydrochloride (DOX) loaded in MSN@Tf@Polymer could be released in 5 h at pH 5.0, which is an improvement from the results obtained at pH 6.5 and pH 7.4. MTT assay and fluorescence inversion microscope experiments indicate that MSN@Tf is successfully taken up by liver cancer cells (Huh7) without apparent cytotoxicity, and Tf has strong intensity of fluorescence for subcellular localization. Confocal laser scanning microscopy (CLSM) experiments indicate that MSN@Tf@Polymer is able to enter the lysosome of the tumor cells. Furthermore, cell apoptosis experiments prove that DOX loaded in MSN@Tf@Polymer has the best anti-tumor effect compared with free DOX and DOX in bare MSN. MSN@Tf@Polymer has high biocompatibility, enhanced drug loading, site-specific delivery and in situ stimulus release and will also hopefully be applied as an intracellular drug delivery system.