2025-02-17 作者：ZJ 来源：文献：Dual-modal imaging-guided theranostic nanocarriers based on 2-methoxyestradiol and indocyanine green-ScienceDirect
文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=1k060re0mw5v02c0p25x0410tc195709&site=xueshu_se
作者：Nan Zhang, Yue Xu, Xiangying Xin, Pengchao Huo, Yan Zhang, Hui Chen, Nannan Feng, Quanling Feng, Zhenzhong Zhang
相关产品：
DSPE-PEG2K 二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000
cRGDyk-DSPE-PEG2K cRGDyk肽-二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000
cholesterol 胆固醇
原文摘要：Drug toxicity and insufficient drug dosing place a limit on the effect of chemotherapy. Optimal efficacy is achieved by exposing tumor cells to the maximum tolerated dose of a chemotherapeutic drug. In this study, we developed a strategy (graphic summary) for enhancing the therapeutic and diagnostic capabilities of known chemotherapeutics. We used a dual-mode near-infrared (NIR) fluorescence/photoacoustic imaging technology to achieve actively guided tumor targeting of the photothermal therapeutic agent indocyanine green (ICG) and the
chemotherapeutic drug 2-methoxyestradiol (2-ME), which were loaded into thermosensitive liposomes (TSLs) with surface-grafted tumor-targeting peptide cRGDyk (cRGDyk-2-ME@ICG-TSLs). In vitro studies demonstrated that cRGDyk-2-ME@ICG-TSLs effectively induced drug accumulation and cytotoxicity in NIR laser-irradiated B16-F10 melanoma cells using dual targeting based on the cRGDyk peptide and temperature sensitivity. An in vivo study showed that 24 h after intravenously injecting cRGDyk-2-ME@ICG-TSLs into melanoma tumor-bearing mice, the dual-mode NIR fluorescence/photoacoustic imaging could accurately identify tumors and normal tissues. In addition, the combination of cRGDyk-2-ME@ICG-TSLs and NIR radiation suppressed tumor growth in tumor-bearing nude mice and was associated with a low risk of side effects on normal organs. Our results indicate that TSLs are a suitable drug delivery system for diagnostic and chemotherapeutic agents guided by dual-mode imaging.
cRGDyk-DSPE-PEG2K在结构上，DSPE作为疏水性成分，能与脂质环境良好亲和，为材料与细胞膜等相互作用奠定基础。PEG2K（聚乙二醇分子量2000）具有出色的亲水性，可提高材料在水性环境中的稳定性和溶解性，减少在体内的免疫原性和非特异性吸附，延长循环时间。cRGDyk是靶向功能单元，它是一种环肽，能特异性识别整合素αvβ3。该材料可用于构建靶向化合物递送系统，将化合物装载其中。通过cRGDyk与整合素αvβ3的特异性结合，实现对tumor等部位的准确靶向给药，提高化合物在靶部位的浓度，增强效果。该文献使用双模式近红外（NIR）荧光/光声成像技术，实现了吲哚菁绿（ICG）和2-甲氧基雌二醇（2-ME）的引导tumor靶向，它们与表面移植的tumor靶向肽cRGDyk（cRGDyk-2-ME@ICG-TSLs）加载到热敏脂质体（TSLs）中。
图：B16-F10细胞与FITC、FITC-FITC（适合）或cRGDyk-FITC-TSLs（CFIT）孵育的共聚焦显微镜图像（CLSM）
用脂质水合法制备cRGDyk-2-ME@ICG-TSLs
TSLs由薄膜分散方法使用脂质混合包含DPPC、胆固醇、磷脂聚乙二醇（DSPE-PEG2K）和磷脂聚乙二醇-RGD肽（cRGDyk-DSPE-PEG2K）以一个定义的摩尔比。将脂质混合物加入到一个茄子状的反应瓶中。将ICG和2-ME同时添加到溶解在氯仿和甲醇中的脂质混合物中。混合物被超声处理，然后在旋转蒸发器上蒸发至干燥，形成薄膜。然后，将PBS（pH = 7.4）加入到含有干燥膜的茄形反应瓶中进行水化。将浓缩分散体在室温下保持，然后用超声处理。将挤压后的TSLs用含有十月烷基硫酸钠的PBS透析，以去除游离化合物和有机溶剂。利用聚碳酸酯薄膜对cRGDyk-2- ME@ICG-TSL制备物的尺寸分布进行了优化。cRGDyk-2-ME-TSLs和cRGDyk-ICGTSLs采用相同的方法制备。
图：在37◦C-42◦C下，ICG@ICG-TSLs的体外化合物释放量
结论：DPPC、胆固醇、磷脂聚乙二醇（DSPE-PEG2K）和（cRGDyk-DSPE-PEG2K）参与制备的cRGDyk-2-ME@ICG-TSLs基于cRGDyk肽和温度敏感性，可有效诱导NIR激光照射的B16-F10细胞中的化合物积累。研究表明，双模式NIR荧光/光声成像可以准确识别tumor和正常组织。此外，cRGDyk-2-ME@ICG-TSLs和NIR辐射联合使用抑制了tumor生长。
