Magnetite nanocluster and paclitaxel-loaded charge-switchable nanohybrids for MR imaging and chemotherapy

Highly efficient accumulation of nanoscaled theranostic agents in a tumor site is crucial for cancer diagnosis and therapy. In this study, we designed a drug-loaded charge-switchable nanohybrid system (HNPs-DA) triggered by the low pH value of tumor microenvironment (pH 6.5) to enhance the uptake efficiency of NPs in cancer cells; the nanohybrid could exhibit T2-MR imaging enhancement and chemotherapy ability, ascribed to the loaded magnetite nanocluster (MNC) and paclitaxel (PTX), respectively. The HNPs-DA comprises two distinct functional components: (1) a biocompatible amphiphilic polymer (Pluronic F127) to act as a nanovehicle for MNC and PTX after self-assembly in an aqueous solution; and (2) a hydrophilic polymeric shell derived from stearoyl-polyethylenimine-2,3-dimethylmalefic anhydride (SC-g-PEI-DMMA). SC-g-PEI-DMMA switches the surface charge of the HNPs-DA from negative to positive by diminishing the anionic part of DMMA and sequentially recovering the cationic instinct of the PEI part at pH 6.5, which could facilitate the cellular uptake and therefore enhance the theranostic effects. In vitro studies demonstrated a darker T2-MRI image in the HNPs-DA-treated HepG2 cells at pH 6.5 as compared to that at pH 7.4. Moreover, CCK8 assay indicated that HNPs-DA exhibited a much higher cytotoxicity against HepG2 cells at pH 6.5, and flow cytometric analysis suggested that the cell death induced by HNPs-DA occurred via apoptosis, which was detected by Annexin V antibody and propidium iodide staining.