文献：

Indocyanine green conjugated lipid microbubbles as an ultrasound-responsive drug delivery system for dual-imaging guided tumor-targeted therapy

文献链接：

作者：

Yan Li, Wenqi Huang，Chunyan Li and Xiaoteng Huang

相关产品：

DSPE-PEG2000–ICG（磷脂-聚乙二醇2000-吲哚菁绿）

原文摘要：

Herein, a multifunctional traceable and ultrasound-responsive drug targeted delivery system based on indocyanine green (ICG) and folic acid (FA) covalently conjugated lipid microbubbles (ILMBs–FA) is proposed. After encapsulation of the anticancer drug resveratrol (RV), the composite (RILMBs–FA) with fluorescence and ultrasound imaging capacity was studied for highly sensitive dual-imaging guided tumor targeted therapy. The resulting RILMBs–FA with an average particle size of 1.32  0.14 mm exhibited good stability and biocompatibility characteristics. The RILMBs–FA featured a high RV loading ratio and the encapsulated RV has been demonstrated to be released from the microbubbles triggered by ultrasound (US) waves. In addition, it was found that the linked FA could facilitate a high cellular uptake of RILMBs–FA via the FA receptor-mediated endocytosis pathway. Compared to free RV and RILMBs, RILMBs–FA with US irradiation demonstrated a more significant tumor cell-killing efficacy mediated by apoptosis in vitro. Eight hours post intravenous injection of RILMBs–FA, the composites showed maximum accumulation in tumorous tissues according to in vivo fluorescence and US images. This ultimately led to the best tumor inhibition effect among all tested drugs under US irradiation. In vivo biosafety evaluations showed that RILMBs–FA featured high biocompatibility characteristics and no significant systemic toxicity over the course of one month. Taken in concert, these results demonstrate the versatility of this drug delivery system with dual-imaging and ultrasound-triggered drug release characteristics for potential future applications in cancer theranostics.

DSPE-PEG2000-ICG：DSPE是一种磷脂，具有亲水性的磷酸乙醇胺头部和两条疏水性的硬脂酰脂肪酸链。因为其磷脂结构可以与细胞膜相互作用，DSPE常被用于构建脂质体等纳米载体，有利于递送等应用。PEG2000代表聚乙二醇（Polyethylene glycol），其分子量约为 2000。聚乙二醇是一种具有良好水溶性和生物相容性的聚合物。它可以增加分子的亲水性，减少蛋白质吸附和免疫原性。在这种化合物中，PEG 链连接在 DSPE 上，起到空间位阻和稳定分子的作用，防止纳米粒子的聚集等。ICG：是吲哚菁绿（Indocyanine Green）的缩写。它是一种近红外荧光染料，最大吸收和发射波长在近红外区域（780 - 820nm 左右）。因为近红外光在生物组织中的穿透深度相对较大，并且生物组织在这个波段自身荧光干扰较少，所以 ICG 是一种很有价值的生物成像试剂。基于此，该文献研究了一种新材料：RILMBs-FA的合成如下：

图：RILMBs-FA的合成及应用

ICG和FA偶联和rv负载的MBs（RILMBs-FA）的制备：

DSPC，RV（溶解在DMSO），DSPE-PEG2000-ICG和DSPE-PEG2000-FA以一定的摩尔比混合三氯甲烷中混合， 在氮气条件下去除溶剂。在真空下进一步去除多余的三氯甲烷。干燥的磷脂混合物在磷酸盐缓冲盐水（PBS）中水合。然后向混合物中加入C3F8。最后，将外加剂机械振动。将制备的MBs用PBS溶液在桶式转子中洗涤，离心以去除多余的未结合的脂质，然后在去离子水中透析以去除未结合的RV和多余的DMSO。获得了ICG和FA偶联和rv负载的MBs（RILMBs-FA）。同时也制备了不含RV的RILMBs-FA（ILMBs-FA）作为对比剂。此外，当DSPE-PEG-FA被DSPE-PEG取代后，按照RILMBs-FA的类似制备方法制备了无FA的RILMBs-FA（RILMBs）。

图：产品表征图像

结论：

该文献提出了一种基于吲哚菁绿（ICG）和叶酸（FA）共价偶联脂质微泡（RILMBs-FA）的多功能可追踪超声响应药物靶向递送系统，并基于DSPE-PEG2000-ICG成功制备出RILMBs-FA。结果证明，这种具有双成像和超声触发药物释放特性的药物传递系统的多功能性，在cancerTreatment 中具有潜在的未来应用。