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：Xiaojuan Pang, Jinping Wang, Xiaoxiao Tan, Fang Guo, Mingzhu Lei, Man Ma, Meng Yu, Fengping Tan and Nan Li

相关产品：DSPE-PEG2000-FA 磷脂-聚乙二醇2000-叶酸

原文摘要：The development of treatment protocols that resulted in a complete response to photothermal therapy (PTT) was usually hampered by uneven heat distribution and low effectiveness. Here, we reported an NIR fluorescence and photoacoustic dual-modal imaging-guided active targeted thermal sensitive liposomes (TSLs) based on the photothermal therapy agent Indocyanine green (ICG) and antiangiogenesis agent Rapamycin (RAPA) to realize enhanced therapeutic and diagnostic functions. As expected, the in vitro drug release studies exhibited the satisfactory result of drug released from the TSLs under hyperthermia conditions induced by NIR stimulation. The in vitro cellular studies confirmed that the FA-ICG/RAPA-TSLsplus NIR laser exhibited efficient drug accumulation and cytotoxicity in tumor cells and epithelial cells. After 24 h intravenous injection of FA-ICG/RAPA-TSLs, the margins of tumor and normal tissue were accurately identified via the in vivo NIR fluorescence and photoacoustic dual-modal imaging. In addition, FA-ICG/RAPATSLs combined with NIR irradiation treated tumor-bearing nude mice inhibited tumor growth to a great extent and possessed much lower side effects to normal organs. All detailed evidence suggested that the theranostic TSLs which were capable of enhancing the therapeutic index might be a suitable drug delivery system for dual-modal imaging-guided therapeutic tools for diagnostics as well as the treatment of tumors.

DSPE-PEG2000-FA包含了DSPE、PEG2000和叶酸（FA）三个重要部分。DSPE是一种磷脂，赋予了材料与细胞膜良好的相互作用能力，有助于其在生物膜相关环境中的应用。PEG2000具有高度的亲水性，，同时减少在体内的非特异性吸附。叶酸（FA）则是靶向功能基团，许多tumor细胞表面过度表达叶酸受体，DSPE-PEG2000-FA能够通过叶酸与这些受体特异性结合，从而实现对tumor细胞的靶向作用。基于此该文献报道了一种NIR荧光和光声双模态成像引导的活性靶向热敏感脂质体（TSLs），结合ICG（ICG）和（RAPA），以实现增强的效果和功能。过程如下：

图：FA-ICG/RAPA-TSLs的(a)结构和FAICG/RAPA-TSLs的(b)作用机制

FA-ICG/RAPA-TSLs的制备。

采用薄膜蒸发和水合法制备了由DPPC：Chol：DSPE-PEG2000：2DSPE 2000-FA组成的温敏脂质体（TSLs）。将溶解在甲醇中的ICG和RAPA加入到脂质混合物中，然后将其干燥成薄膜。

简单地说，将ICG、RAPA、DPPC、DSPE-PEG2000、DSPE-PEG2000- FA和Chol分别溶解在氯仿和甲醇中，放在圆底烧瓶中。然后使用旋转蒸发器蒸发溶剂，在烧瓶壁上形成脂膜。水化方法主要包括以下步骤：首先在室温下加入PBS（pH=7.4），然后在室温下机械摇晃浓缩分散体，超声，最后用聚碳酸酯膜进一步纯化FA-ICG/RAPA-TSLs。然后PBS透析去除任何未结合的化合物分子和有机溶剂。

图：(a) HeLa细胞和ICG/DIO-TSLs和FA-ICG/DIO-TSLs分别经激光照射和不经激光照射孵育后的(a) HeLa细胞和(b) HUVECs的共聚焦图像

结论：DSPE-PEG2000-FA参与制备的温敏脂质体（FA-ICG/RAPA-TSLs），用于NIR荧光和光声双模态成像引导下的协同作用。该系统在以下几个方面具有优越性：首先，将ICG和RAPA以较高的封装效率纳入TSLs，克服自由体的缺点；第二，FA-ICG/RAPA-TSLs作为应用探针跟踪tumor区域，这对激光束聚焦在tumor区域并将NIR光能充分转化为热有作用；第三，ICG的PTT效应可以增强TSLs中RAPA的释放，从而发挥作用。