Chiang Hao-Han, Chang Yu-Teng, Huang Wei-Ren, Cai Min-Xuan, Feng Chin-Hsing, Syu Jia-Ning, Lai Chih-Sheng, Chien Yi-Hsin
Department of Materials Science and Engineering, Feng Chia University, Taichung 40724, Taiwan.
Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
ACS Appl Bio Mater. 2025 Sep 15;8(9):7783-7792. doi: 10.1021/acsabm.5c00769. Epub 2025 Aug 27.
Targeted imaging of the lymphatic system is essential for the early diagnosis and management of lymphatic disorders, such as lymphedema. In this study, we developed a lymphatic-targeted fluorescent nanoprobe by encapsulating indocyanine green (ICG) within poly(lactic--glycolic acid) (PLGA) nanoparticles, further surface-modified with hyaluronic acid-polyethylene glycol (HA-PEG) to enhance specificity (HA-PEG-ICG/PLGA NPs). The nanoparticles were synthesized a microemulsion technique followed by surface cross-linking, and thoroughly characterized by ultraviolet-visible (UV-vis) spectroscopy, fluorescence emission analysis, Fourier transform infrared (FTIR) spectroscopy, and ζ-potential measurements, confirming their physicochemical stability and functionalization. cytotoxicity assays indicated excellent biocompatibility with both human keratinocytes (HaCaT) and mouse lymphatic endothelial cells (SVEC4-10). Confocal microscopy and quantitative fluorescence analyses revealed significantly enhanced uptake of HA-PEG-ICG/PLGA NPs in SVEC4-10 cells, which was attributed to HA-mediated binding to LYVE-1 receptors. imaging in C57BL/6JCrlBltw mice further demonstrated prolonged retention and selective fluorescence accumulation in lymphatic vessels following intraperitoneal administration, surpassing those of free ICG and ICG/PLGA controls. Collectively, these results confirm the potential of HA-PEG-ICG/PLGA NPs as a safe and effective nanoplatform for real-time lymphatic imaging. This targeted system holds promises for early lymphedema diagnosis, intraoperative lymphatic mapping, and future integration with theragnostic strategies for lymphatic-associated diseases.
淋巴系统的靶向成像对于淋巴疾病（如淋巴水肿）的早期诊断和管理至关重要。在本研究中，我们通过将吲哚菁绿（ICG）封装在聚乳酸-乙醇酸（PLGA）纳米颗粒中，进一步用透明质酸-聚乙二醇（HA-PEG）进行表面修饰以提高特异性，从而开发了一种淋巴靶向荧光纳米探针（HA-PEG-ICG/PLGA NPs）。纳米颗粒采用微乳液技术合成，随后进行表面交联，并通过紫外可见（UV-vis）光谱、荧光发射分析、傅里叶变换红外（FTIR）光谱和ζ电位测量进行全面表征，证实了它们的物理化学稳定性和功能化。细胞毒性试验表明，其与人角质形成细胞（HaCaT）和小鼠淋巴管内皮细胞（SVEC4-10）均具有良好的生物相容性。共聚焦显微镜和定量荧光分析显示，SVEC4-10细胞对HA-PEG-ICG/PLGA NPs的摄取显著增强，这归因于HA介导的与LYVE-1受体的结合。在C57BL/6JCrlBltw小鼠体内成像进一步表明，腹腔注射后，淋巴管中HA-PEG-ICG/PLGA NPs的保留时间延长且荧光选择性积累，超过了游离ICG和ICG/PLGA对照。总体而言，这些结果证实了HA-PEG-ICG/PLGA NPs作为实时淋巴成像安全有效纳米平台的潜力。这种靶向系统有望用于早期淋巴水肿诊断、术中淋巴管造影以及未来与淋巴相关疾病的诊疗策略相结合。
