Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 380-702, Korea.
Department of Green Bio Engineering, Korea National University of Transportation, Chungju 380-702, Korea.
Int J Mol Sci. 2019 Oct 28;20(21):5368. doi: 10.3390/ijms20215368.
Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π-π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy.
在这里，我们描述了基于二醇染料偶联荧光聚合物点（L-PD）的碳化二硫化物核交联聚合物点的制备和表征，该聚合物点具有 pH 可裂解的比色纳米传感器，用于在荧光成像引导的肿瘤化学疗法中进行还原触发的紫杉醇（PTX）释放。L-PD 通过π-π 堆积或疏水相互作用装载 PTX（PTX 负载的 L-PD），以通过在肿瘤中高浓度谷胱甘肽（GSH）存在下二硫键的断裂来选择性地进行治疗诊断，从而增强 PTX 的释放。在生理条件下，纳米杂化体系表现出荧光猝灭行为，释放的 PTX 少于 2%。然而，在肿瘤微环境中，在酸性 pH 下荧光恢复，并且通过肿瘤细胞中 GSH 水平引起的还原，PTX（约 100%的药物释放）从基质中有效地释放出来，从而提高了癌症治疗的效果。因此，该比色纳米传感器有望根据周围 pH 值和 GSH 浓度在正常组织和癌变组织之间进行区分，以便将 PTX 选择性递送至癌细胞中，从而改善癌症诊断和化疗效果。
