Kim Won Young, Won Miae, Koo Seyoung, Zhang Xingcai, Kim Jong Seung
Department of Chemistry, Korea University, Seoul, 02841, Korea.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
Nanomicro Lett. 2021 Aug 5;13(1):168. doi: 10.1007/s40820-021-00689-1.
The insistent demand for space-controllable delivery, which reduces the side effects of non-steroidal anti-inflammatory drugs (NSAIDs), has led to the development of a new theranostics-based approach for anti-inflammatory therapy. The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker, hydrogen polysulfide (HS). Here, we report a novel theranostic agent 1 (TA1), consisting of three parts: HS-mediated triggering part, a two-photon fluorophore bearing mitochondria targeting unit (Rhodol-TPP), and anti-inflammatory COX inhibitor (indomethacin). In vitro experiments showed that TA1 selectively reacts with HS to concomitantly release both Rhodol-TPP and indomethacin. Confocal-microscopy imaging of inflammation-induced live cells suggested that TA1 is localized in the mitochondria where the HS is overexpressed. The TA1 reacted with HS in the endogenous and exogenous HS environments and in lipopolysaccharide treated inflammatory cells. Moreover, TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E (PGE) level in blood serum from inflammation-induced mouse models. In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic effects, showing its function as a theranostic agent, capable of both anti-inflammatory therapy and precise diagnosis. Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.
对空间可控给药的迫切需求，这种给药方式可减少非甾体抗炎药（NSAIDs）的副作用，已促使一种基于诊疗一体化的抗炎治疗新方法得以发展。通过设计一种对炎症部位生物标志物多硫化氢（HS）有响应的药物递送系统，可以改进当前的抗炎治疗方法。在此，我们报告了一种新型诊疗试剂1（TA1），它由三部分组成：HS介导的触发部分、带有线粒体靶向单元的双光子荧光团（罗丹明-TPP）以及抗炎COX抑制剂（吲哚美辛）。体外实验表明，TA1与HS选择性反应，同时释放罗丹明-TPP和吲哚美辛。对炎症诱导的活细胞进行共聚焦显微镜成像显示，TA1定位于HS过表达的线粒体中。TA1在内源性和外源性HS环境以及脂多糖处理的炎症细胞中均能与HS反应。此外，TA1可抑制炎症诱导细胞中的COX-2水平以及炎症诱导小鼠模型血清中的前列腺素E（PGE）水平。对炎症诱导小鼠模型进行的体内实验表明，TA1表现出炎症部位选择性药物释放，并随后产生显著的治疗效果，显示出其作为一种诊疗试剂的功能，能够同时进行抗炎治疗和精确诊断。TA1的诊疗行为在炎症性疾病的体内模型治疗中具有高度适用性。
