Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, Hubei Engineering Research Center for Advanced Fine Chemicals , School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, P. R. China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, P. R. China.
J Nanosci Nanotechnol. 2021 Dec 1;21(12):5965-5971. doi: 10.1166/jnn.2021.19514.
Facile preparation of a tumoral-stimuli-activated theranostic nanoparticle with simple constituents remains a challenge for tumor theranostic nanosystems. Herein we design a simple reductionresponsive turn-on theranostic nanoparticle for achieving fluorescent imaging and phototherapy combination. The theranostic nanoparticle is prepared by a simple one-step dialysis method of reduction active amphiphilic hyperbranched poly(-amidoamines) and a near-infrared (NIR) dye indocyanine green (ICG). The fluorescence of ICG is quenched by the aggregation-caused quenching (ACQ) effect. The fluorescent intensity of free ICG at 816 nm was ∼40 times as high as that of particulate ICG. After reductive nanoparticles incubated with dithiothreitol (DTT), the size of the nanoparticles increased from 160 nm to 610 nm by Dynamic light scattering (DLS). As nanoparticles were internalized by cancer cells, the disulfide bonds would be cleaved by intracellular reduction agents like glutathione (GSH), leading to the release of entrapped ICG. The released ICG regained its fluorescence for self-monitoring the release and therapeutic effect of ICG by fluorescence spectra and the quantitative evaluation of NIR fluorescence intensity. Remarkably, nanoparticles can also reinforce antitumor efficacy through photodynamic therapy and GSH depletion property. This study provides new insights into designing turn-on theranostic systems.
简单成分的肿瘤刺激激活治疗诊断一体化纳米粒子的制备仍然是肿瘤治疗诊断纳米系统的一个挑战。在此，我们设计了一种简单的还原响应型开启治疗诊断一体化纳米粒子，以实现荧光成像和光疗的联合应用。该治疗诊断一体化纳米粒子通过还原活性两亲性超支化聚（聚酰胺-胺）和近红外染料吲哚菁绿（ICG）的简单一步透析法制备。ICG 的荧光被聚集诱导猝灭（ACQ）效应猝灭。游离 ICG 在 816nm 处的荧光强度约为颗粒状 ICG 的 40 倍。用二硫苏糖醇（DTT）孵育还原纳米粒子后，纳米粒子的粒径通过动态光散射（DLS）从 160nm 增加到 610nm。当纳米粒子被癌细胞内化时，二硫键会被细胞内还原剂如谷胱甘肽（GSH）切断，导致包埋的 ICG 释放。通过荧光光谱和近红外荧光强度的定量评估，释放的 ICG 恢复其荧光，用于自我监测 ICG 的释放和治疗效果。值得注意的是，纳米粒子还可以通过光动力治疗和 GSH 耗竭特性增强抗肿瘤疗效。本研究为设计开启治疗诊断系统提供了新的思路。
