文献：Near-infrared nanoparticles based on indocyanine green-conjugated albumin: a versatile platform for imaging-guided synergistic tumor chemophototherapy with temperature-responsive drug release

文献链接：https://xueshu.baidu.com/usercenter/paper/show?paperid=1y290j50hr550240hk2u0my0xg678990&site=xueshu_se

作者：Yuxin Ma,Xiaohua Liu,Qianli Ma,Yizhi Liu

相关产品：Sulfo ICG-NHS酯

原文摘要：Background: The aim of this study was to develop a multifunctional theranostic agent based on BSA nanoparticles (NPs), which loaded artemisinin (ART) and co-conjugated with indocyanine green (ICG) and arginine-glycine-aspartic acid (RGD) peptide (RGD-indocyanine green-Bovine Serum Albumin- artemisinin [IBA] NPs).

Materials and methods: The physicochemical parameters of RGD-IBA NPs were characterized in terms of the particle size, zeta potential, morphology, entrapment efficiency, drug loading,

in vitro release behavior, photothermal and photodynamic effect, and in vitro anticancer ability.

In vivo fluorescence and thermal imaging as well as antitumor studies were also evaluated.

Results: The tumor chemotherapeutic effects of ART and the ability of fluorescence imaging,

hyperthermia generation and reactive oxygen species production of ICG and tumor-targeting RGD

were integrated to achieve RGD-IBA NPs for imaging-guided tumor-targeted chemotherapy/

photothermal/photodynamic therapy (chemo-phototherapy). The RGD-IBA NPs showed enhanced physiological stability and photo-stability compared with free ART and ICG. In addition, they were temperature-responsive; their sizes increased with increasing temperature between 25°C and 55°C, thereby leading to drug release upon the irradiation with near infrared (NIR) laser. In vivo fluorescence images of tumor-bearing mice showed that the RGD-IBA NPs could highly and passively reach the targeted tumor region with maximum accumulation at 24 hours post-intravenous injection. The in vitro and in vivo results demonstrated that the RGD-IBA NPs not only have good biocompatibility, but also are highly efficient tumor synergistic chemo-phototherapeutic agents.

Conclusion: Through this study, it was found that RGD-IBA NPs could potentially be a very

promising tumor theranostic agent.

磺基 ICG-NHS 酯是一种粉末状的化学物质。其主要成分包括吲哚菁绿（ICG）、磺酸基以及活性酯基团（NHS）。磺基的引入提高了其水溶性。在性能方面，磺基 ICG-NHS 酯具有近红外荧光特性。它可以与生物分子中的氨基等基团发生共价结合，从而实现对生物分子的标记。这种标记后的生物分子在近红外光激发下会发出荧光信号，便于进行检测和追踪。磺基 ICG-NHS 酯可用于活体荧光成像等方面。它能够提供高灵敏度和高分辨率的检测手段，有助于深入了解生物体内的生理过程。基于BSA纳米颗粒（NPs）的多功能应用，该颗粒负载青蒿素（ART），并与吲哚菁绿（ICG）和精氨酸甘氨酸（RGD）肽（RGD-青蒿氨酸青牛血清白蛋白-青蒿素[IBA] NPs）共结合。制备过程如下：

图：合成及应用原理图

RGD-ICG-BSA-ART NPs的制备过程：

将ART在DMSO中溶解，并分散到 BSA溶液中，磁性搅拌。总共用戊二醛进行交联。然后，用蒸馏水（MW切断=12 kDa）透析，以纯化BSA-ART溶液。然后，将磺基ICG-NHS酯加入到BSA-ART溶液中，搅拌，得到ICG-BSA-ART溶液。然后，将氨基-PEG2,000-RGD分散到ICG-BSA-ART溶液中EDC和 NHS。混合物轻微搅拌反应，用蒸馏水透析，得到RGD-ICG-BSA-ART NPs（RGDIBA NPs）。

图：PBS、游离ICG、IBA NPs和RGD-IBA NPs在808 nm激光NIR照射5分钟下的温度变化曲线。

结论：磺基ICG-NHS酯参与制备的RGD-IBA NPs，用于成像引导下的协同应用。使用NIR照射可以通过同时产生热疗、产生ROS和化合物的释放来促进RGD-IBA NPs与BSA NPs偶联，提高了ART和ICG在水溶液中的稳定性。利用ICG的荧光特性，RGD-IBA NPs可以通过体内成像系统监测ICG的行为。在体外和体内的结果表明基于RGD-IBA NPs的CHT/PTT/PDT联合应用具有协同作用。此外，RGD-IBA NPs在体内外均无明显的细胞有害性。