School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, P. R. China.
CAS Key Laboratory of Nano-Bio Interface, Suzhou Key Laboratory of Functional Molecular Imaging Technology, Division of Nanobiomedicine andi-Lab, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
Angew Chem Int Ed Engl. 2020 Apr 27;59(18):7219-7223. doi: 10.1002/anie.202000947. Epub 2020 Mar 10.
Activatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side-effects. Herein, a tumor microenvironment (TME)-activated NIR-II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self-assembling the peptide Fmoc-His, mercaptopropionic-functionalized Ag S quantum dots (MPA-Ag S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR-II fluorescence "off" state, because of Ag S QDs-A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc-His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME-activated theranostic strategy holds great promise for future clinical applications.
由于具有高检测特异性、有效消融和最小副作用等特点，激活型诊断与治疗系统在肿瘤的诊断和治疗方面显示出巨大的应用潜力。本研究构建了一种基于肿瘤微环境（TME）激活的近红外二区（NIR-II）纳米诊疗一体化系统（FEAD1），用于腹腔转移的精准诊断与治疗。FEAD1 由 Fmoc-His 肽、巯基丙酸功能化的 Ag S 量子点（MPA-Ag S QDs）、化疗药物阿霉素（DOX）和 NIR 吸收剂 A1094 自组装而成。研究表明，在健康组织中，由于 Ag S QDs-A1094 相互作用，FEAD1 处于 NIR-II 荧光“关闭”状态，而 DOX 则处于隐形状态。FEAD1 递送至肿瘤部位后，酸性 TME 通过破坏 Fmoc-His 金属配位和 DOX 疏水相互作用触发其解组装。A1094 的释放使 Ag S 荧光开启，从而照亮肿瘤，同时在肿瘤组织内爆发式释放 DOX，实现肿瘤的精准诊断与治疗。这种 TME 激活型诊疗策略具有广阔的临床应用前景。
