Abstract
Objectives 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. Methods 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. Results 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. Conclusions 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.
Highlights
Osteosarcoma is the most common primary malignant tumor in both children and adolescents and accounts for about 35% of malignant bone tumors [1]
After 72 h of exposure to low concentrations of carbon quantum dots (CQDs) (69 and 138 μg/ml), the viability of 143B cells was not significantly altered; cells exposed to the higher concentration of CQDs (276 μg/ml) showed a significant decrease in proliferation (Figures 1(c)–1(e))
These results indicate that CQDs decreased cellular viability and increased the apoptosis rate
Summary
Osteosarcoma is the most common primary malignant tumor in both children and adolescents and accounts for about 35% of malignant bone tumors [1]. With the development of limb-salvaging surgery, neoadjuvant chemotherapy, immunotherapy, gene therapy, molecular targeted therapy, and other comprehensive treatments, the BioMed Research International. 5-year survival rate of osteosarcoma patients has increased to more than 80% [2]. Such treatments have several deficiencies, such as cancer recurrence, incision infection, high expense, and side effects [3]. Carbon-based nanomaterials have been studied for biomedical applications in recent years. Carbon nanomaterials have attracted attention due to their unique physicochemical and biological effects, such as low density, good chemical stability, low price, low toxicity, and strong cell penetration [4]. Few studies have demonstrated that carbon-based nanomaterials present different cellular effects
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