Sun Ping, Gao Chunlei, Chen Zhe, Wang Siyu, Li Gang, Luan Mingming, Wang Yaoguang
School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
Shanghai Wanhou Biotechnology Co., Ltd., Shanghai 201815, China.
Biosensors (Basel). 2025 Jun 13;15(6):383. doi: 10.3390/bios15060383.
Developing appropriate methods for real-time in situ investigation of how drugs influence signaling pathways and related biomolecules holds enormous potential for helping to provide an understanding of how anticancer drugs exert their effects. Herein, we report a smart nanoprobe, PDA-MB (DOX)-Pep, constructed on the basis of polydopamine nanoparticles (PDA NPs) modified with a dense shell of molecular beacon (MB) with embedded doxorubicin (DOX) and peptide, which can respond specifically to miRNA-34a and Caspase-3 targets. Intracellular experiments demonstrated that, in comparison to the control nanoprobe PDA-MB-Pep, the smart nanoprobe could selectively respond to miRNA-34a, facilitating the release of the embedded DOX. The released DOX subsequently activated the p53 pathway, which further upregulated miRNA-34a expression, leading to additional DOX release. This initiated a cyclical process involving the probe's response to miRNA-34a, DOX release, p53 activation, and miRNA-34a upregulation, ultimately enhancing cell apoptosis and increasing Caspase-3 expression. The designed smart nanoprobe offers a visual approach to explore how anticancer drugs influence signaling pathways and related molecules at the cellular level.
开发适用于实时原位研究药物如何影响信号通路和相关生物分子的方法，对于帮助理解抗癌药物的作用机制具有巨大潜力。在此，我们报告了一种智能纳米探针PDA-MB(DOX)-Pep，它基于用嵌入阿霉素(DOX)和肽的分子信标(MB)致密壳修饰的聚多巴胺纳米颗粒(PDA NPs)构建，可对miRNA-34a和Caspase-3靶点产生特异性响应。细胞内实验表明，与对照纳米探针PDA-MB-Pep相比，该智能纳米探针可选择性地响应miRNA-34a，促进嵌入DOX的释放。释放的DOX随后激活p53通路，进一步上调miRNA-34a表达，导致更多DOX释放。这启动了一个循环过程，包括探针对miRNA-34a的响应、DOX释放、p53激活和miRNA-34a上调，最终增强细胞凋亡并增加Caspase-3表达。所设计的智能纳米探针为在细胞水平探索抗癌药物如何影响信号通路和相关分子提供了一种可视化方法。
