Hu Yong, Wang Ruizhi, Zhou Yiwei, Yu Nuo, Chen Zhigang, Gao Dongmei, Shi Xiangyang, Shen Mingwu
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China.
J Mater Chem B. 2018 Oct 14;6(38):6122-6132. doi: 10.1039/c8tb01870g. Epub 2018 Sep 10.
We present the development of indocyanine green (ICG)-loaded and folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs) as a versatile nanoplatform for targeted dual-mode fluorescence (FL)/photoacoustic (PA) imaging, and photothermal therapy (PTT)/photodynamic therapy (PDT) of tumors in vivo. In this study, acid-treated MWCNTs with carboxyl residues were first covalently conjugated with polyethyleneimine (PEI). This was followed by sequential modification of FA via a polyethylene glycol (PEG) segment, fluorescein isothiocyanate (FITC), and succinic anhydride (SAH), multifunctional FA-modified MWCNTs (MWCNT-PEI·SAH-FITC-PEG-FA) were formed. The functional MWCNTs possess exceptional colloidal stability, good hemocompatibility/cytocompatibility in a studied concentration range, and targeting specificity to FA receptor-overexpressing cancerous cells. Viaπ-π stacking interactions, the MWCNTs enable highly efficient loading of ICG and the ICG-loaded MWCNTs exhibit excellent photostability and can be used for FL imaging/PDT of tumors due to the singlet oxygen (O) generation from ICG. In addition, the near-infrared absorption characteristic of ICG also renders the MWCNT nanoplatform with a capacity for simultaneous PA imaging and PTT of tumors. Our study reports a novel theranostic nanosystem that can be used for targeted dual-mode FL/PA imaging and PTT/PDT of tumors in vivo, which may show profound promise for translation into clinical uses.
我们展示了负载吲哚菁绿(ICG)和叶酸(FA)修饰的多壁碳纳米管(MWCNT)的开发,作为一种多功能纳米平台,用于体内肿瘤的靶向双模荧光(FL)/光声(PA)成像以及光热疗法(PTT)/光动力疗法(PDT)。在本研究中,首先将具有羧基残基的酸处理MWCNT与聚乙烯亚胺(PEI)共价共轭。随后通过聚乙二醇(PEG)链段、异硫氰酸荧光素(FITC)和琥珀酸酐(SAH)依次修饰FA,形成了多功能FA修饰的MWCNT(MWCNT-PEI·SAH-FITC-PEG-FA)。功能性MWCNT具有出色的胶体稳定性,在研究浓度范围内具有良好的血液相容性/细胞相容性,以及对过表达FA受体的癌细胞的靶向特异性。通过π-π堆积相互作用,MWCNT能够高效负载ICG,负载ICG的MWCNT表现出优异的光稳定性,并且由于ICG产生单线态氧(O),可用于肿瘤的FL成像/PDT。此外,ICG的近红外吸收特性还使MWCNT纳米平台具有同时进行肿瘤PA成像和PTT的能力。我们的研究报道了一种新型的治疗诊断纳米系统,可用于体内肿瘤的靶向双模FL/PA成像以及PTT/PDT,这可能在转化为临床应用方面显示出巨大的前景。