Reduction-Responsive Nanocarrier Co-delivery Indomethacin and Doxorubicin for Overcoming Multi-drug Resistant Breast Cancer
- VernacularTitle: 还原响应型纳米载体共递送多柔比星和吲哚美辛逆转乳腺癌多药耐药
- Author:
Zhen-Yu YAN
1
Author Information
- Publication Type:Journal Article
- Keywords: Co-delivery; Hyaluronic acid; Indomethacin; Multidrug resistance; Reduction-responsive
- From: Chinese Pharmaceutical Journal 2020;55(11):925-932
- CountryChina
- Language:Chinese
- 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.
