College of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
Biomacromolecules. 2024 Aug 12;25(8):4991-5007. doi: 10.1021/acs.biomac.4c00415. Epub 2024 Aug 1.
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 -cleavage of CRISPR/Cas13a, initiating its -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.
GPS-纳米载体（MA-NV@DOX-Cas13a）是一种针对黑色素瘤的成像和基因/化疗协同治疗的靶向纳米平台。它利用滚环扩增（RCA）产物作为支架构建 DNA“纳米载体”（NV），其中包含多价适体（MA）作为“GPS”，将阿霉素（DOX）封装在载体中，并配备 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，使 MA-NV@DOX-Cas13a 能够通过受体介导的内吞作用进行靶向成像和精确递药。癌细胞中信号转导和转录激活因子 3（STAT3）的激活触发 CRISPR/Cas13a 的切割，从而启动其切割功能。此外，脱氧核糖核酸酶 I（DNase I）降解 MA-NV，释放 DOX 进行细胞内成像和作为化疗药物。实验证明了这种多功能纳米平台在细胞成像和联合治疗方面的卓越性能，同时突出了这些纳米药物递送系统在减轻 DOX 副作用方面的优势。
