在肺癌化疗过程中，药物的长期使用经常造成多药耐药现象，我们设计了一种肺癌部位富集、药物释放速度可控、肿瘤细胞内ATP响应、化药/基因双组分协同的耐药肺癌治疗策略。首先进行载阿霉素的ATP核酸适配体（DOX-Duplex）的构建；其次以阳离子聚合物PEI为载体，将DOX-Duplex与耐药蛋白抑制剂miR-519c进行共组装，形成双组分协同的化药/基因共载纳米复合物（DOX-Duplex/PEI/miR-519c）；最后以酸敏感性高分子材料PCADK与PLGA为基质，制备装载DOX-Duplex/PEI/miR-519c纳米复合物的可吸入式多孔微球。我们对多孔微球的基本性质进行表征，在细胞水平和动物水平上研究其抑制肿瘤增殖、降低药物外排的效果及作用机制，并进行大鼠体内药动学、药代学、药物分布和毒理学研究。我们希望通过这项工作为耐药肺癌治疗的研究与临床应用提供新的策略。

In the process of lung cancer chemotherapy, the long-term use of drugs often causes multidrug resistance. We designed a strategy for the treatment of lung cancer with high concentration of lung cancer, controllable drug release rate, ATP response in tumor cells and synergistic combination of drug and gene. Firstly, the doxorubicin loaded ATP aptamer (DOX-Duplex) was constructed; Secondly, the cationic polymer PEI was used as the carrier to assemble the DOX-Duplex and the drug resistance protein inhibitor miR-519c, constructing the DOX-Duplex/PEI/miR-519c; Finally, the porous DOX-Duplex/PEI/miR-519c microspheres were prepared using PCADK and PLGA as matrix. The basic properties of porous microspheres were characterized. The ability and mechanism of inhibiting tumor proliferation and reducing drug efflux were studied in vitro and in vivo. Then, the pharmacokinetics, pharmacokinetics, drug distribution and toxicology in rats were studied. We hope that this work will provide a new strategy for the research and clinical application of drug resistant lung cancer treatment.