药物输送
癌细胞
纳米技术
癌症治疗
癌症研究
适体
化学
肺癌
DNA
靶向给药
细胞
纳米结构
癌症
分子生物学
材料科学
生物
病理
医学
内科学
生物化学
作者
Ning Wang,Chang Sik Yu,Tingting Xu,Dan Yao,Lingye Zhu,Zhifa Shen,Xiaoying Huang
标识
DOI:10.1186/s12951-022-01701-5
摘要
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.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.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 significant suppression of cell proliferation, invasion and migration, and also enhanced cell apoptosis due to the excellent performance of drug delivery and intracellular release, while maintaining a superior biosafety. In addition, the antitumor effects of Apt-NS-DOX were further confirmed using in vivo models.Our study provided cell-specific aptamer-modified DNA nanostructures as a drug-delivery system targeting A549 cells, which could precisely and efficiently transport chemotherapeutic drug into tumor cells, exerting enhanced antineoplastic efficacy. These findings highlight that DNA nanostructure serving as an ideal drug delivery system in cancer treatment appears great promise in biomedical applications.
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