Song Xinyue, Yan Tao, Tian Feng, Li Fengyan, Ren Linlin, Li Qiong, Zhang Shusheng
Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Chemistry and Chemical Engineering, Linyi University, Shandong, China.
Materials Science and Engineering, Mobile Postdoctoral Center, Qingdao University, Shandong, China.
Front Bioeng Biotechnol. 2021 Feb 22;9:639487. doi: 10.3389/fbioe.2021.639487. eCollection 2021.
As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.
作为一种广泛使用的抗癌药物，阿霉素（DOX）主要通过干扰DNA活性诱导细胞死亡；因此，DOX主要在细胞核中发挥治疗作用。然而，大多数已报道的药物递送系统在细胞核中缺乏良好的定位，而是将DOX分子释放到细胞质中。由于核膜形成的巨大屏障，只有约1%的DOX能够到达细胞核并保持活性。因此，为了达到理想的治疗效果，不可避免地要过量使用DOX分子，这会引发严重的副作用。在此，我们开发了一种高度定位的药物纳米载体，用于将DOX分子释放到其作用位点，在该位点DOX分子可直接干扰DNA活性。在这项工作中，我们使用阳离子聚合物修饰的上转换纳米颗粒（UCNPs）作为发光核心和基因载体，同时适配体作为装载DOX的DNA纳米列车。最终，所制备的纳米诊疗剂表现出良好的靶向性，在浓度远低于DOX半数致死浓度（LC50）的情况下具有高达93.04%的高细胞凋亡率，并且对肿瘤生长具有明显的抑制作用。
