文献：Multi-layered tumor-targeting photothermaldoxorubicin releasing nanotubes eradicate tumors in vivo with negligible systemic toxicity

文献链接：https://pubmed.ncbi.nlm.nih.gov/29694478/

作者：Daquan Wang, Lingjie Meng, Zhaofu Fei, Chen Hou, Jiangang Long,Leli Zeng,Paul J. Dyson and Peng Huang

相关产品：FA-PEG-SH（叶酸-聚乙二醇-巯基）

原文摘要：

Multi-layered single-walled carbon nanotubes, termed SWNT@BSA@Au-S-PEG-FA@DOX, which integrate photothermal therapy with small molecule drug delivery, were prepared using a facile layer-by-layer assembly process. Oxidized and cut single-walled carbon nanotubes (SWNTs) were coated with bovine serum albumin (BSA) to provide abundant active sites for the nucleation of Au seeds, which are subsequently converted into gold nanoparticles (Au NPs) by in situ reduction. The resulting SWNT@BSA@Au material exhibits ideal photothermal properties. Further modification of the nanomaterial with folic acid terminated-polyglycol (FA-PEG-SH) and subsequent loading with doxorubicin (DOX) afford the SWNT@BSA@Au-S-PEG-FA@DOX. The FA terminated PEG endows the material with high water-dispersibility, biocompatibility and cancer cell selectivity. A high drug loading ratio for DOX of up to 590% was achieved, with the drug release being pH and temperature dependent, adding to the selectivity of the system. High efficacy of the SWNT@BSA@Au-S-PEG-FA@DOX material, when combined with photothermal therapy (irradiation of the tumor with an 808 nm laser, 1 W cm−2 for 5 min, 24 h after systemic injection of the nanomedicine), was demonstrated in vivo, resulting in complete tumor eradication. Remarkably, the side effects are negligible with only minor damage to normal tissues including the liver and kidneys being observed.   

FA-PEG-SH:叶酸是一种水溶性维生素，它在人体生理过程中发挥着重要的作用，主要参与 DNA 合成和细胞分裂等过程。从化学结构上来看，叶酸含有一个对氨基苯甲酸（PABA）部分、一个蝶啶环和一个谷氨酸残基。PEG（聚乙二醇）聚乙二醇是一种常见的聚合物，具有良好的亲水性、生物相容性和低poison性。在这个化合物中，PEG 起到连接和修饰的作用。其分子量大小会影响整个分子的一些性质，如溶解性、在体内的循环时间等。SH（巯基）巯基（-SH）是一个具有较高化学活性的官能团。它能够参与多种化学反应，如氧化还原反应、与金属离子的配位反应和形成二硫键等。这种化学反应活性使得 FA - PEG - SH 可以作为一种多功能的中间体，用于构建更复杂的分子结构或化合物递送系统。基于FA - PEG - SH的相关性能，多层单壁碳纳米管SWNT@BSA@Au-S-PEG-FA@DOX的合成如下：

图：合成示意

将SWNT@BSA@Au水溶液与FA-PEG-SH水溶液混合，在室温下搅拌。用超滤装置收集SWNT@BSA@Au-S-PEG-FA材料，用水洗涤，去除未反应的FA-PEG-SH。SWNT@BSA@Au-S-PEG-FA材料在水中重新分散。此外，SWNT@BSA@Au-S-PEGm（即不含FA）采用相同的程序制备，但用mPEG-SH取代了FA-PEG-SH前体。水分散SWNT@BSA的-@Au-S-PEG-FA和各种数量的盐酸阿霉素混合在PBS缓冲溶液在搅拌下。将得到的红色悬浮液在室温下搅拌。收集SWNT@BSA@Au-S-PEG-FA@DOX产物，将上清液反复超离心，用 PBS缓冲液洗涤，直至上清液无色。未吸收的透明上清液的数量是通过测量透明上清液在DOX的特征吸光度处的吸光度相对于在相同条件下记录的校准曲线来确定的，从而估算DOX的负荷。

图：电镜图像

结论：

该文献成功制备出基于FA - PEG - SH合成的多层单壁碳纳米管SWNT@BSA@Au-S-PEG-FA@DOX。该材料由于金外骨骼的存在，具有较高的光热转换效率，能在水中很好地分散，具有生物相容性，在药理应用中也具有重要的特性。