基于滚环扩增的自组装形成“GPS-纳米传送器”，用于体外靶向成像和增强基因/化疗 (CRISPR/DOX) 协同治疗。
Rolling Circle Amplification-Based Self-Assembly to Form a "GPS-Nanoconveyor" for In Vitro Targeted Imaging and Enhanced Gene/Chemo (CRISPR/DOX) Synergistic Therapy.
发表日期：2024 Aug 12
作者：
Huan Du, Fang Wang, Ruyan Zhang, Xiaoyan Yan, Jinfeng Zheng, Ting Zhou, Xiufeng Wang, Guodong Zhang, Zhiqing Zhang
来源：
BIOMACROMOLECULES
摘要：
GPS-Nanoconveyor (MA-NV@DOX-Cas13a) 是一种靶向纳米平台，专为黑色素瘤的成像和基因/化疗协同治疗而设计。它利用滚环扩增（RCA）产品作为支架构建DNA“纳米传送器”（NV），其中包含多价适体（MA）作为“GPS”，将阿霉素（DOX）封装在转运蛋白中，并为其配备CRISPR/Cas13a 核糖核蛋白 (Cas13a RNP)。携带MA增强了识别B16细胞上过表达的受体核仁素的能力，从而能够通过受体介导的内吞作用实现靶向成像和精确递送MA-NV@DOX-Cas13a。癌细胞中信号转导子和转录激活子 3 (STAT3) 的激活触发 CRISPR/Cas13a 的顺式切割，启动其反式切割功能。此外，脱氧核糖核酸酶 I (DNase I) 会降解 MA-NV，释放 DOX 用于细胞内成像并作为化疗剂。实验证明了这种多功能纳米平台在细胞成像和协同治疗方面的卓越能力，同时突出了这些纳米药物输送系统在减轻 DOX 副作用方面的优势。
The GPS-Nanoconveyor (MA-NV@DOX-Cas13a) is a targeted nanoplatform designed for the imaging and gene/chemotherapy synergistic treatment of melanoma. It utilizes rolling circle amplification (RCA) products as a scaffold to construct a DNA "Nanoconveyor" (NV), which incorporates a multivalent aptamer (MA) as a "GPS", encapsulates doxorubicin (DOX) in the transporter, and equips it with CRISPR/Cas13a ribonucleoproteins (Cas13a RNP). Carrying MA enhances the ability to recognize the overexpressed receptor nucleolin on B16 cells, enabling targeted imaging and precise delivery of MA-NV@DOX-Cas13a through receptor-mediated endocytosis. The activation of signal transducer and activator of transcription 3 (STAT3) in cancer cells triggers cis-cleavage of CRISPR/Cas13a, initiating its trans-cleavage function. Additionally, deoxyribonuclease I (DNase I) degrades MA-NV, releasing DOX for intracellular imaging and as a chemotherapeutic agent. Experiments demonstrate the superior capabilities of this versatile nanoplatform for cellular imaging and co-treatment while highlighting the advantages of these nanodrug delivery systems in mitigating DOX side effects.