State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
Department of Chemistry and Biochemistry, Florida International University, Miami, FL, 33199, USA.
Adv Healthc Mater. 2024 May;13(12):e2303710. doi: 10.1002/adhm.202303710. Epub 2024 Feb 11.
Diagnosing and treating liver fibrosis is a challenging yet crucial endeavor due to its complex pathogenesis and risk of deteriorating into cirrhosis, liver failure, and even hepatic cancer. Herein, a silica cross-linked micelles (SCLMs) based nano-system is developed for both diagnosing and treating liver fibrosis. The SCLMs are first modified with peptide CTCE9908 (CT-SCLMs) and can actively target CXCR4, which is overexpressed in activated hepatic stellate cells (HSCs). To enable diagnosis, an ONOO-responded near-infrared fluorescent probe NOF2 is loaded into the CT-SCLMs. This nano-system can target the aHSCs and diagnose the liver fibrosis particularly in CCl-induced liver damage, by monitoring the reactive nitrogen species. Furthermore, a step is taken toward treatment by co-encapsulating two anti-fibrosis drugs, silibinin and sorafenib, within the CT-SCLMs. This combined approach results in a significant alleviation of liver injury. Symptoms associated with liver fibrosis, such as deposition of collagen, expression of hydroxyproline, and raised serological indicators show notable improvement. In summary, the CXCR4-targeted nano-system can serve as a promising theragnostic system of early warning and diagnosis for liver fibrosis, offering hope against progression of this serious liver condition.
诊断和治疗肝纤维化是一项具有挑战性但至关重要的任务,因为其发病机制复杂,有恶化为肝硬化、肝衰竭甚至肝癌的风险。在此,我们开发了一种基于硅交联胶束(SCLMs)的纳米系统,用于肝纤维化的诊断和治疗。首先,SCLMs 被肽 CTCE9908(CT-SCLMs)修饰,能够主动靶向在活化的肝星状细胞(HSCs)中过表达的 CXCR4。为了实现诊断,我们将一种 ONOO-响应的近红外荧光探针 NOF2 载入 CT-SCLMs 中。该纳米系统可以通过监测活性氮物种,靶向 aHSCs 并诊断肝纤维化,特别是在 CCl 诱导的肝损伤中。此外,我们还通过共包封两种抗纤维化药物水飞蓟素和索拉非尼,进一步实现治疗。这种联合方法显著减轻了肝损伤。与肝纤维化相关的症状,如胶原沉积、羟脯氨酸表达和血清学指标升高,均有明显改善。总之,这种靶向 CXCR4 的纳米系统可以作为肝纤维化预警和诊断的有前途的治疗学系统,为治疗这种严重的肝脏疾病提供了希望。
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