Department of Orthopedic Surgery, Peking University First Hospital, Beijing 100034, China.
School of Materials Science and Engineering, Beihang University, Beijing 100191, China.
Biomed Res Int. 2020 Jul 10;2020:2846297. doi: 10.1155/2020/2846297. eCollection 2020.
Carbon-based nanomaterials have gained attention in the field of biomedicine in recent years, especially for the treatment of complicated diseases such as cancer. Here, we report a novel carbon-based nanomaterial, named carbon quantum dots (CQDs), which has potential for cancer therapy. We performed a systematic study on the effects of CQDs on the osteosarcoma 143B cell line in vitro and in vivo.
Cell counting assay, the neutral red assay, lactic dehydrogenase assay, and fluorescein isothiocyanate (FITC) Annexin V/Propidium iodide (PI) were used to detect the cytotoxicity and apoptosis of CQDs on the 143B cell line. Intracellular reactive oxygen species (ROS) were detected by the oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate. The JC-10 assay was used to detect the mitochondrial membrane potential (MMP) of 143B cells incubated with CQDs. The effects of CQDs on the 143B cell line were evaluated by Western blot and immunofluorescence analysis of apoptosis-related proteins Bax, Bcl-2, cytochrome-C, caspase-3, cleaved-caspase-3, PARP1, and cleaved-PARP1. Male tumor-bearing BALB/c nude mice were used to investigate the antitumor effects of CQDs, and the biosafety of CQDs in vivo was tested in male BALB/c mice by measuring weight changes, hematology tests, and histological analyses of major organs.
CQDs exhibited a high cytotoxicity and induced apoptosis toward the 143B cell line. CQDs can also significantly increase the intracellular level of ROS and lower the mitochondrial membrane potential levels of 143B cells. CQDs increase apoptotic protein expression to induce apoptosis of 143B cells by triggering the mitochondrial apoptotic signaling pathway. The tumor volume in the CQD-treated mice was smaller than that in the control group, the tumor volume inhibition rate was 38.9%, and the inhibitory rate by tumor weight was 30.1%. All biosafety test indexes were within reference ranges, and neither necrosis nor inflammation was observed in major organs.
CQDs induced cytotoxicity in the 143B cell line through the mitochondrial apoptotic signaling pathway. CQDs not only showed an antitumor effect but also high biocompatibility in vivo. As a new carbon-based nanomaterial, CQDs usage is a promising method for novel cancer treatments.
近年来，碳基纳米材料在生物医药领域引起了关注，特别是在治疗癌症等复杂疾病方面。本研究报告了一种新型碳基纳米材料，即碳量子点（CQDs），其在癌症治疗方面具有潜在应用价值。我们对 CQDs 在体外和体内对骨肉瘤 143B 细胞系的作用进行了系统研究。
采用细胞计数法、中性红法、乳酸脱氢酶法和异硫氰酸荧光素（FITC） Annexin V/碘化丙啶（PI）检测 CQDs 对 143B 细胞系的细胞毒性和细胞凋亡作用。采用氧化敏感荧光探针 2'，7'-二氯荧光素二乙酸检测细胞内活性氧（ROS）。采用 JC-10 法检测 CQDs 孵育后 143B 细胞的线粒体膜电位（MMP）。通过 Western blot 和凋亡相关蛋白 Bax、Bcl-2、细胞色素 C、caspase-3、cleaved-caspase-3、PARP1 和 cleaved-PARP1 的免疫荧光分析评估 CQDs 对 143B 细胞系的作用。采用雄性荷瘤 BALB/c 裸鼠研究 CQDs 的抗肿瘤作用，并通过测量体重变化、血液学检查和主要器官组织学分析，检测 CQDs 在体内的生物安全性。
CQDs 对 143B 细胞系表现出高细胞毒性，并诱导其凋亡。CQDs 还可以显著增加 143B 细胞内 ROS 水平，并降低线粒体膜电位水平。CQDs 通过触发线粒体凋亡信号通路增加凋亡蛋白表达，诱导 143B 细胞凋亡。与对照组相比，CQD 处理组的肿瘤体积较小，肿瘤体积抑制率为 38.9%，肿瘤重量抑制率为 30.1%。所有生物安全性测试指标均在参考范围内，主要器官未见坏死或炎症。
CQDs 通过线粒体凋亡信号通路诱导 143B 细胞系的细胞毒性。CQDs 不仅在体内显示出抗肿瘤作用，而且具有高生物相容性。作为一种新型碳基纳米材料，CQDs 的应用为新型癌症治疗方法提供了一种有前途的手段。
