Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
University of Science and Technology of China, Hefei 230026, China.
Biomater Sci. 2023 Jun 27;11(13):4664-4674. doi: 10.1039/d3bm00249g.
Acute liver injury (ALI), induced by an imbalance of pro-inflammatory and anti-inflammatory processes, remains a major concern for disease detection and drug screening. However, current clinical blood tests for ALI diagnostics are limited by delayed estimation, invasive and non-comprehensive visualization and false results from non-specific biomarkers. Moreover, it is difficult to give timely therapy to inhibit its progression and adjust treatment regimens in time. Herein, this study developed a facile theragnostic nano-platform (BLD NP) for effective treatment and real-time imaging of acute liver injury (ALI). BLD NPs comprise peptide-caged NIR probes (CyGb) for real-time imaging and a small molecular drug (dexamethasone sodium phosphate, Dsp) for timely treatment of ALI, in which CyGb was conjugated and Dsp was electrostatically complexed with fluorinated polyethylene (LPOF), respectively. After systemic administration, BLD NPs passively target liver tissue and react with ALI-associated protease to activate the NIR signaling moiety for non-invasive longitudinal imaging of ALI progression, while Dsp is released timely for ALI treatments, serving as a theragnostic platform and providing comprehensive estimations for ALI, comparable to standard methods including blood tests and flow cytometric analysis. Therefore, BLD NPs hold great promise for early real-time imaging, timely therapeutic treatment and prediction of the progression of ALI.
急性肝损伤(ALI)是由促炎和抗炎过程失衡引起的,仍然是疾病检测和药物筛选的主要关注点。然而,目前用于 ALI 诊断的临床血液检测受到延迟估计、侵入性和非全面可视化以及非特异性生物标志物结果不准确的限制。此外,很难及时给予治疗以抑制其进展并及时调整治疗方案。在此,本研究开发了一种简便的治疗和实时成像急性肝损伤(ALI)的诊断纳米平台(BLD NP)。BLD NPs 由肽笼状近红外探针(CyGb)组成,用于实时成像,小分子药物(地塞米松磷酸钠,Dsp)用于及时治疗 ALI,其中 CyGb 与氟化聚乙烯(LPOF)进行共轭连接,而 Dsp 则通过静电复合的方式与之结合。在系统给药后,BLD NPs 被动靶向肝脏组织,并与与 ALI 相关的蛋白酶反应,以激活近红外信号部分,用于非侵入性的 ALI 进展的纵向成像,同时 Dsp 也能及时释放,用于 ALI 的治疗,作为一种治疗和诊断平台,可提供与包括血液检测和流式细胞分析在内的标准方法相当的全面评估。因此,BLD NPs 有望用于早期实时成像、及时治疗以及预测 ALI 的进展。