Self-assembly of DNA nanostructure containing cell-specific aptamer as a precise drug delivery system for cancer therapy in non-small cell lung cancer

作者：Ning Wang, Chang Sik Yu, Tingting Xu, Dan Yao, Lingye Zhu, Zhifa Shen, Xiaoying Huang · 发表于：Journal of Nanobiotechnology · 年份：2022 · DOI：10.1186/s12951-022-01701-5 · 被引用次数：25 · 研究领域：Advanced biosensing and bioanalysis techniques、Nanoparticle-Based Drug Delivery、Cancer therapeutics and mechanisms

BACKGROUND: As the most common subtype in lung cancer, the precise and efficient treatment for non-small cell lung cancer (NSCLC) remains an outstanding challenge owing to early metastasis and poor prognosis. Chemotherapy, the most commonly used treatment modality, is a difficult choice for many cancer patients due to insufficient drug accumulation in tumor sites and severe systemic side-effects. In this study, we constructed a cell-specific aptamer-modified DNA nanostructure (Apt-NS) as a targeting drug delivery system achieving the precision therapy for lung cancer. METHODS: The synthesis of DNA nanostructure and its stability were evaluated using gel electrophoresis. The targeting properties and internalization mechanism were investigated via flow cytometry and confocal analyses. Drug loading, release, and targeted drug delivery were determined by fluorescence detection, Zeta potentials assay, and confocal imaging. CCK8 assays, colony formation, cell apoptosis, metastasis analyses and in vivo experiments were conducted to assess the biological functions of DNA nanostructure. RESULTS: Self-assembled DNA nanoparticles (Apt-NS) had excellent stability to serum and DNase I and the ability to specifically recognize A549 cells. Upon specific binding, the drug-loaded nanoparticles (Apt-NS-DOX) were internalized into target cells by clathrin-mediated endocytosis. Subsequently, DOX could be released from Apt-NS-DOX based on the degradation of the lysosome. Apt-NS-DOX exerted signif...