用于双光子生物成像和体内肿瘤治疗的具有本征活性氧物种放大的多酚碳量子点。
Polyphenolic Carbon Quantum Dots with Intrinsic Reactive Oxygen Species Amplification for Two-Photon Bioimaging and In Vivo Tumor Therapy.
发表日期:2023 Oct 31
作者:
Sayan Deb Dutta, Md Moniruzzaman, Jin Hexiu, Sourav Sarkar, Keya Ganguly, Dinesh K Patel, Jagannath Mondal, Yong-Kyu Lee, Rumi Acharya, Jongsung Kim, Ki-Taek Lim
来源:
Cell Death & Disease
摘要:
最近的研究表明,线粒体功能障碍和 DNA 损伤对细胞存活有着至关重要的影响,这被认为是癌症治疗的治疗靶点之一。在这项研究中,我们展示了多酚碳量子点(CQD)对体外和体内抗肿瘤功效影响的比较研究。由容易获得的无毒前体(间苯三酚)合成双发射(绿色和黄色)形状特异性多酚 CQD(G-CQD 和 Y-CQD),并与圆形蓝色探针相比,研究了合成探针的抗肿瘤特性源自广泛报道的前体柠檬酸和尿素的发射性 CQD(B-CQD)。 B-CQD 具有细胞核靶向特性,G-CQD 和 Y-CQD 具有线粒体靶向特性。我们发现,含有多酚的 CQD(剂量为 100 μg mL-1)通过过量积累来特异性攻击线粒体,改变新陈代谢,抑制分支模式,失衡 Bax/Bcl-2 稳态,最终产生氧化应激水平,导致体外氧化应激诱导癌细胞死亡。我们表明,G-CQD 是癌细胞氧化应激的主要原因,因为它们能够产生足够的·OH- 和 1O2 自由基,电子顺磁共振波谱和对苯二甲酸测试证明了这一点。此外,CQD 在双光子(TP)发射中表现出近红外吸收特性,可用于癌细胞的 TP 细胞成像,无需光漂白。体内抗肿瘤试验进一步揭示,瘤内注射G-CQDs可显着增强皮下肿瘤的治疗效果,且对BalB/c裸鼠无任何不良影响。我们相信基于形状特异性多酚 CQD 的纳米治疗剂在肿瘤治疗中具有潜在作用,从而证明了对恶性癌症治疗的见解。
Recent studies indicate that mitochondrial dysfunctions and DNA damage have a critical influence on cell survival, which is considered one of the therapeutic targets for cancer therapy. In this study, we demonstrated a comparative study of the effect of polyphenolic carbon quantum dots (CQDs) on in vitro and in vivo antitumor efficacy. Dual emissive (green and yellow) shape specific polyphenolic CQDs (G-CQDs and Y-CQDs) were synthesized from easily available nontoxic precursors (phloroglucinol), and the antitumor property of the as-synthesized probe was investigated as compared to round-shaped blue emissive CQDs (B-CQDs) derived from well-reported precursor citric acid and urea. The B-CQDs had a nuclei-targeting property, and G-CQDs and Y-CQDs had mitochondria-targeting properties. We have found that the polyphenol containing CQDs (at a dose of 100 μg mL-1) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced Bax/Bcl-2 homeostasis, and ultimately generating oxidative stress levels, leading to oxidative stress-induced cell death in cancer cells in vitro. We show that G-CQDs are the main cause of oxidative stress in cancer cells because of their ability to produce sufficient •OH- and 1O2 radicals, evidenced by electron paramagnetic resonance spectroscopy and a terephthalic acid test. Moreover, the near-infrared absorption properties of the CQDs were exhibited in two-photon (TP) emission, which was utilized for TP cellular imaging of cancer cells without photobleaching. The in vivo antitumor test further discloses that intratumoral injection of G-CQDs can significantly augment the treatment efficacy of subcutaneous tumors without any adverse effects on BalB/c nude mice. We believe that shape-specific polyphenolic CQD-based nanotheranostic agents have a potential role in tumor therapy, thus proving an insight on treatment of malignant cancers.