Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.
Int J Nanomedicine. 2022 Apr 2;17:1567-1575. doi: 10.2147/IJN.S337082. eCollection 2022.
Multifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery.
Disulfide-functionalized dicyanomethylene-4-pyran (DCM-SS-NH) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation-responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π-π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs.
Experimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX.
The fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.
基于肿瘤靶向和细胞内监测的多功能纳米载体近年来受到了研究人员的广泛关注和深入研究。在本研究中，我们报告了基于聚多巴胺纳米粒子（NPs）的多功能糖基纳米粒子，该纳米粒子具有可激活的近红外探针，用于肿瘤成像和靶向药物传递。
巯基化二氰基乙烯-4-吡喃（DCM-SS-NH）和氨基化乳糖分别通过迈克尔加成或席夫碱反应修饰并负载在聚多巴胺纳米粒子（NPs）表面，作为 GSH 刺激响应荧光探针和肿瘤靶向部分。阿霉素（DOX）作为一种模型抗癌药物，通过π-π相互作用直接负载到聚多巴胺上，制备多功能 PLDD（PDA@Lac/DCM/DOX） NPs。
实验结果表明，成功制备了 PLDD NPs。在 GSH 浓度为 5 mM 的溶液中，DCM 的荧光在 PLDD NPs 中被猝灭，能够恢复红色荧光。在弱酸性环境（pH 5）下，PLDD NPs 中 DOX 的释放量在 72 小时内达到 44%。CLSM 和流式细胞术的结果表明，由于 NPs 上乳糖衍生物与 HepG2 细胞膜上过表达的去唾液酸糖蛋白受体之间的特殊识别，PLDD NPs 具有良好的 HepG2 靶向能力。更重要的是，DCM-SS-NH 中的二硫键在癌细胞内高浓度 GSH 的作用下被破坏，激活了用于癌细胞成像的近红外荧光探针 DCM。MTT 测定表明，与游离 DOX 相比，PLDD NPs 对 HepG2 细胞具有更高的抗癌效率，并且对正常细胞的副作用降低。
负载在 PLDD NPs 上的修饰 DCM 的荧光能够在癌细胞内高浓度 GSH 环境中恢复，同时提高化疗效果，降低副作用。它为肿瘤成像和靶向药物传递的整合提供了一个很好的例子。
