Reduction-Responsive Nanocarrier Co-delivery Indomethacin and Doxorubicin for Overcoming Multi-drug Resistant Breast Cancer / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare a reduction-responsive nanoparticle (HID-NPs) for indomethacin (IND) and doxorubicin (DOX) delivering and investigate their effects on reversing multidrug resistance in breast cancer. METHODS: Hyaluronic acid-based amphiphilic substances (HA-SS-PA) were prepared by amidation reaction, and their structures were confirmed by NMR. HID-NPs were prepared by nano-precipitation method. The particle size measurement and morphology observation of the HID-NPs were measured by dynamic light scanning (DLS) and transmission electron microscopy (TEM), respectively. The reduction-responsive drug release behavior of HID-NPs was determined by dialysis method. Cell uptake HID-NPs on human breast cancer MCF-7/ADR cells were observed by laser confocal microscopy. The cytotoxicity of HID-NPs on human breast cancer MCF-7 and MCF-7/ADR cells was determined by MTT assay. RESULTS: 1H-NMR spectrum indicated that HA-SS-PA was successfully prepared. The results of DLS and TEM showed that HID-NPs were round and evenly distributed with an average particle size of (103±3.2) nm. Drug release assay indicates that HID-NPs have good reduction-responsiveness ability. Cell uptake experiments demonstrated that HID-NPs significantly increased DOX accumulation in MCF-7/ADR cells compared with free DOX; MTT assays showed that HID-NPs could significantly destroy MCF-7/ADR cells. CONCLUSION: HID-NPs shows good reduction-responsiveness and obvious reverse DOX resistance, which can be used for the treatment of multidrug resistance of breast tumors.