Hyperbranched polymers functionalized magnetic nanoparticles for targeted delivery and intracellular release of cisplatin

To address the obstacles facing the clinical use of cisplatin (cis-diamminedichloroplatinum(II) (CDDP)), including poor bioavailability, severe dose-limiting side effects and rapid development of drug resistance, a novel pH-sensitive superparamagnetic drug delivery system was developed based on hyperbranched poly(ethylene glycol-b-citric acid) modified Fe3O4 nanoparticles (Fe3O4@PCA-b-PEG) for targeted delivery and pH-triggered intracellular release of cisplatin. The Fe3O4@PCA(CDDP)-b-PEG nanoparticles exhibit excellent water dispersity with well-defined size distribution (around 49.5 nm) and strong magnetisability. In vitro release experiments revealed that the CDDP-loaded delivery system is relatively stable at physiologic conditions (pH 7.4 and 37 ˚C) but susceptible to acidic environments (pH 5.3 and 37 ˚C) which would trigger the release of loaded drugs. Fluorescent microscope studies revealed that the Fe3O4@PCA(CDDP)-b-PEG nanoparticles could be efficiently accumulate in tumor tissue. Also, in comparison with CDDP, the Fe3O4@PCA(CDDP)-b-PEG exert higher cytotoxicity towards the human cervical cancer HeLa cells and the Human breast cancer MDA-MB-231 cells. The results indicate that the prepared superparamagnetic Fe3O4@PCA(CDDP)-b-PEG nanoparticles are a promising candidate for inhibiting proliferation of cancer cells.