Li Fengqiao, Mei Hao, Xie Xiaodong, Zhang Huijuan, Liu Jian, Lv Tingting, Nie Huifang, Gao Yu, Jia Lee
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, 2 Xueyuan Road, Yangguang Building, 6FL., Fuzhou, 350002, Fujian, China.
Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
AAPS J. 2017 May;19(3):814-826. doi: 10.1208/s12248-017-0057-9. Epub 2017 Feb 23.
Lung cancer is the leading cancer and has the highest death rate. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has had a promising response in lung cancer therapy. Unfortunately, individuals with TKI-resistant EGFR mutations often develop acquired resistance against erlotinib. To overcome this resistance, in the present study, we developed liposomes anchored with anti-EGFR aptamer (Apt)-conjugated chitosan (Apt-Cs) as stable carriers to deliver erlotinib to the target. We loaded erlotinib into Apt-Cs-anchored liposomal complexes (Apt-CL-E) and characterized the physicochemistry of Apt-CL-E. The nanoparticles showed good biostability and a binding specificity for EGFR-mutated cancer cells guided by the Apt. The specific binding facilitated the uptake of Apt-CL-E into EGFR-mutated cancer cells. A cytotoxicity study showed an advantage of Apt-CL-E over their nontargeted liposomal counterparts in delivering erlotinib to EGFR-mutated cancer cells, resulting in cell cycle arrest and apoptosis. These results provide a good platform for future in vivo animal studies with Apt-CL-E.
肺癌是主要癌症且死亡率最高。表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）厄洛替尼在肺癌治疗中显示出良好疗效。遗憾的是，具有TKI抗性的EGFR突变个体常对厄洛替尼产生获得性抗性。为克服这种抗性，在本研究中，我们开发了锚定有抗EGFR适配体（Apt）-共轭壳聚糖（Apt-Cs）的脂质体作为稳定载体，将厄洛替尼递送至靶标。我们将厄洛替尼载入锚定有Apt-Cs的脂质体复合物（Apt-CL-E）中，并对Apt-CL-E的物理化学性质进行了表征。纳米颗粒显示出良好的生物稳定性以及在Apt引导下对EGFR突变癌细胞的结合特异性。特异性结合促进了Apt-CL-E被EGFR突变癌细胞摄取。细胞毒性研究表明，在将厄洛替尼递送至EGFR突变癌细胞方面，Apt-CL-E优于其非靶向脂质体对应物，导致细胞周期停滞和细胞凋亡。这些结果为未来使用Apt-CL-E进行体内动物研究提供了良好平台。
