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目的制备pH、还原双重敏感的基于聚酰胺-胺树状大分子(PAMAM)的纳米载体PSSP,用于联合携载化疗药物多柔比星(DOX)及耐药逆转剂依克立达(ELC),同时对其逆转乳腺癌多药耐药的效果进行体外评价。方法采用红外光谱FTIR对载体进行结构表征;共聚焦显微镜考察载药纳米粒在细胞内的释药情况;流式细胞术和MTT实验分别考察联合载药纳米粒对乳腺癌多药耐药的逆转作用以及体外抗肿瘤活性。结果成功制备联合载药PSSP/多柔比星/依克立达纳米粒,并通过细胞实验证实p H、还原双重敏感性。共聚焦定位实验表明载体进入细胞后主要集中在溶酶体,在其酸性条件下促发释药并扩散入核。罗丹明123外排实验表明,依克立达可显著增加MCF-7/ADR细胞内罗丹明123的蓄积量。并且PSSP/多柔比星/依克立达纳米粒对MCF-7/ADR细胞的细胞毒性显著大于游离药多柔比星以及PSSP/多柔比星纳米粒。结论多柔比星和依克立达联载纳米粒逆转乳腺癌多药耐药的效果显著提高,且对肿瘤细胞的毒性增强,是一种有应用前景的抗肿瘤药物递送系统。
OBJECTIVE To prepare pH-sensitive and reductive double-sensitive polyamide-amine dendrimer (PAMAM) -based nanocarrier PSSP for the combined use of chemotherapeutic drug doxorubicin (DOX) and drug- ), While its reversal of breast cancer multi-drug resistance in vitro evaluation. Methods FTIR was used to characterize the structure of the carrier. Confocal microscopy was used to investigate the release of drug-loaded nanoparticles in the cells. Flow cytometry and MTT assay were used to examine the reversal of multidrug resistance in combination with drug-loaded nanoparticles. Role and in vitro antitumor activity. Results The drug-loaded PSSP / doxorubicin / ecumethamine nanoparticles were successfully prepared and the dual sensitivity of p H and reduction was confirmed by cell experiments. Confocal positioning experiments showed that the carrier mainly concentrated in the lysosome after entering the cell, and under its acidic conditions, it can promote drug release and diffuse into the nucleus. Rhodamine 123 efflux assay showed that icriprid significantly increased the accumulation of rhodamine 123 in MCF-7 / ADR cells. And the cytotoxicity of PSSP / doxorubicin / ecumethamine nanoparticles on MCF-7 / ADR cells was significantly greater than that of the free drug doxorubicin and PSSP / doxorubicin nanoparticles. CONCLUSION Doxorubicin and Iclidate-loaded nanoparticles can significantly improve the multidrug resistance of breast cancer cells and increase the toxicity to tumor cells. It is a promising antitumor drug delivery system.