Marshall Laboratory of Biomedical Engineering, Research Center for Biosensor and Nanotheranostic, School of Biomedical Engineering, Health Science Center, Shenzhen University, Guangdong 518060, P. R. China.
Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemical and Bioengineering, University of Science and Technology Beijing, 30 Xueyuan Road, Beijing 100083, China.
Anal Chem. 2024 Apr 16;96(15):5922-5930. doi: 10.1021/acs.analchem.3c05977. Epub 2024 Apr 4.
Mitochondrial therapy is a promising new strategy that offers the potential to achieve precise disease diagnosis or maximum therapeutic response. However, versatile mitochondrial theranostic platforms that integrate biomarker detection and therapy have rarely been exploited. Here, we report a charge-reversal nanomedicine activated by an acidic microenvironment for mitochondrial microRNA (mitomiR) detection and ion-interference therapy. The transporter liposome (DD-DC) was constructed from a pH-responsive polymer and a positively charged phospholipid, encapsulating NaCl nanoparticles with coloading of the aggregation-induced emission (AIE) fluorogens AIEgen-DNA/G-quadruplexes precursor and brequinar (NAB@DD-DC). The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.
线粒体治疗是一种很有前途的新策略，有可能实现精确的疾病诊断或最大的治疗反应。然而，很少有多功能的线粒体治疗学平台被用于整合生物标志物检测和治疗。在这里，我们报告了一种通过酸性微环境激活的可充电纳米医学，用于线粒体 microRNA（mitomiR）检测和离子干扰治疗。由 pH 响应性聚合物和带正电荷的磷脂组成的转载体泡囊（DD-DC），包封了负载有聚集诱导发射（AIE）荧光团 AIEgen-DNA/G-四链体前体和布雷奎纳（NAB@DD-DC）的 NaCl 纳米颗粒。带负电荷的纳米药物确保了良好的血液稳定性和高肿瘤积累，而在肿瘤微环境（TME）和溶酶体中酸性 pH 响应的电荷反转增强了肿瘤细胞的摄取和溶酶体逃逸，从而实现了在线粒体中的积累。随后在线粒体中释放的 Na 不仅有助于形成 mitomiR-494 诱导的 G-四链体，用于 AIE 成像诊断，而且还导致渗透压激增，布雷奎纳增强了渗透压激增，从而实现有效的离子干扰治疗。
