论文部分内容阅读
将聚乙二醇(PEG)以二硫键连接到聚酰胺-胺(PAMAM)树状大分子表面构建还原-pH双重敏感纳米载体(PSSP),再用其包载多药耐药逆转剂依克立达(1)。所得载药纳米粒(PSSP/1)平均粒径(19.3±3.4)nm,z电位(+1.83±0.13)mV,载药量和包封率分别为(7.5±0.9)%和(82.3±3.5)%。体外释放试验表明,PSSP/1纳米粒的释放具有明显的还原和p H敏感性。通过体外毒性试验考察1或PSSP/1纳米粒与多柔比星(2)联合用药对乳腺癌耐药细胞系MCF-7/ADR多药耐药的逆转作用。结果表明,1和PSSP/1纳米粒均能显著增强2对MCF-7/ADR的细胞毒性,呈现出耐药逆转效果。逆转效率随PSSP/1纳米粒中1浓度的升高而增强,呈现剂量依赖关系。并且,PSSP/1纳米粒的耐药逆转效果优于游离1。
Polyethylene glycol (PEG) was disulfide bonded to the surface of polyamide-amine (PAMAM) dendrimer to construct reduced-pH dual-sensitive nanocarrier (PSSP) Krieter (1). The mean diameter of PSSP / 1 nanoparticles was (19.3 ± 3.4) nm, and the z potential was + 1.83 ± 0.13 mV. The drug loading and encapsulation efficiency were (7.5 ± 0.9)% and (82.3 ± 3.5) )%. In vitro release tests showed that the release of PSSP / 1 nanoparticles with significant reduction and p H sensitivity. To investigate the reversal effects of 1 or PSSP / 1 nanoparticles combined with doxorubicin (2) on multidrug resistance in breast cancer cell line MCF-7 / ADR by in vitro toxicity assay. The results showed that 1 and PSSP / 1 nanoparticles could significantly enhance the cytotoxicity of 2 pairs of MCF-7 / ADR, showing a reversal of drug resistance. The reversal efficiency increased with the concentration of PSSP / 1 nanoparticles in a dose-dependent manner. Moreover, the drug resistance reversal effect of PSSP / 1 nanoparticles was better than that of free one.