表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）阻断其下游信号传导，抑制肿瘤细胞的异常增殖与分化、抑制肿瘤生长与进展，已成为非小细胞肺癌（NSCLC）一线治疗手段。但NSCLC易通过靶基因修饰、旁路信号传导激活对EGFR-TKIs治疗产生获得性耐药，其中PDLIM5介导AMPK/mTOR活化诱发肿瘤细胞自噬、维持细胞存活、拮抗EGFR-TKIs是产生耐药的主要机制。超声纳米微泡技术可携载基因、药物经超声控释具靶向特异性。结合NSCLC耐药机制、siRNA技术及我们前期超声微泡技术研究结果，设计携载PDLIM5 siRNA超声纳米微泡靶向阻抑PDLIM5进而抑制由AMPK/mTOR活化介导的肿瘤细胞自噬，增强NSCLC对EGFR-TKIs的敏感性，抑制耐药细胞株或肿瘤的生长，提高NSCLC药物治疗效果，为NSCLC耐药机制研究、开发新的治疗靶点及靶向治疗药物提供新的理论依据和治疗方式。

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could inhibit the proliferation and differentiation of tumor cells via blocking the downstream signaling pathway and have been become a first-line treatment for non-small cell lung cancer (NSCLC). However, NSCLC is prone to get acquired resistance to EFGR-TKIs through target gene modification and alternative pathway activation. PDLIM5 could induce tumor cell autophagy, maintain its survival and antagonize EGFR-TKIs, having been a major mechanism of EGFR-TKIs resistance by activating AMPK/mTOR signaling. Ultrasound nanobubbles with targeting specificity could carry gene/drugs and release in control. Combined mechanisms of NSCLC acquired resistance, siRNA technology and our previous research results of ultrasound microbubbles, we intend to design PDLIM5 siRNA-loaded ultrasound nanobubbles to inhibit PDLIM5 expression to control cell autophagy which mediated by AMPK/mTOR activation. And then enhance the sensitivity of NSCLC to EGFR-TKIs, inhibit the growth of EGFR-resistant cell lines or tumor. Therefore, we hope to provide new approaches and means of treatment for the study of drug resistance mechanisms of NSCLC, development of new therapeutic targets and targeted drugs.