基于石墨相氮化碳量子点的多功能纳米平台用于成像引导及肿瘤靶向的化疗-光动力联合治疗。

A multifunctional nanoplatform based on graphitic carbon nitride quantum dots for imaging-guided and tumor-targeted chemo-photodynamic combination therapy.

机构信息

Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong, 271016, PR China.

Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong, 271016, PR China.

出版信息

Colloids Surf B Biointerfaces. 2021 Mar;199:111549. doi: 10.1016/j.colsurfb.2020.111549. Epub 2020 Dec 31.

Abstract

Graphitic carbon nitride quantum dots (g-CNQDs) have shown great potential in imaging, drug delivery and photodynamic therapy (PDT). However, relevant research on g-CNQDs for PDT or drug delivery has been conducted separately. Herein, we develop a g-CNQDs-based nanoplatform (g-CPFD) to achieve simultaneously imaging and chemo-photodynamic combination therapy in one system. A g-CNQDs-based nanocarrier (g-CPF) is first prepared by successively introducing carboxyamino-terminated oligomeric polyethylene glycol and folic acid onto the surface of g-CNQDs via two-step amidation. The resultant g-CPF possesses good physiological stability, strong blue fluorescence, desirable biocompatibility, and visible light-stimulated reactive oxygen species generating ability. Further non-covalently loaded doxorubicin enables the system with chemotherapy function. Compared with free doxorubicin, g-CPFD expresses more efficient chemotherapy to HeLa cells due to improved folate receptor-mediated cellular uptake and intracellular pH-triggered drug release. Furthermore, g-CPFD under visible light irradiation shows enhanced inhibition on the growth of cancer cells compared to sole chemotherapy or PDT. Thus, g-CPFD exhibits exceptional anti-tumor efficiency due to folate receptor-mediated targeting ability, intracellular pH-triggered drug release and a combined treatment effect arising from PDT and chemotherapy. Moreover, this nanoplatform benefits imaging-guided drug delivery because of inherent fluorescent properties of doxorubicin and g-CPF, hence achieving the goal of imaging-guided chemo-photodynamic combination treatments.

摘要

石墨相氮化碳量子点(g-CNQDs)在成像、药物传递和光动力疗法(PDT)方面显示出巨大的潜力。然而,关于 g-CNQDs 用于 PDT 或药物传递的相关研究是分别进行的。在这里,我们开发了一种基于 g-CNQDs 的纳米平台(g-CPFD),以在一个系统中实现同时成像和化学-光动力联合治疗。首先通过两步酰胺化反应将羧基氨基封端的低聚聚乙二醇和叶酸接枝到 g-CNQDs 表面,制备了基于 g-CNQDs 的纳米载体(g-CPF)。所得的 g-CPF 具有良好的生理稳定性、强的蓝光荧光、理想的生物相容性和可见光刺激的活性氧生成能力。进一步非共价负载阿霉素使该系统具有化疗功能。与游离阿霉素相比,由于叶酸受体介导的细胞摄取和细胞内 pH 触发的药物释放增强,g-CPFD 对 HeLa 细胞表现出更有效的化疗作用。此外,与单独的化疗或 PDT 相比,g-CPFD 在可见光照射下对癌细胞的生长具有更强的抑制作用。因此,g-CPFD 由于叶酸受体介导的靶向能力、细胞内 pH 触发的药物释放以及 PDT 和化疗的联合治疗效果,表现出优异的抗肿瘤效率。此外,由于阿霉素和 g-CPF 的固有荧光特性,该纳米平台有利于成像引导药物传递,从而实现成像引导的化学-光动力联合治疗的目标。

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