Dutta Sayan Deb, Moniruzzaman Md, Hexiu Jin, Sarkar Sourav, Ganguly Keya, Patel Dinesh K, Mondal Jagannath, Lee Yong-Kyu, Acharya Rumi, Kim Jongsung, Lim Ki-Taek
Department of Biosystems Engineering, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea.
Institute of Forest Science, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea.
ACS Appl Mater Interfaces. 2023 Nov 15;15(45):52083-52099. doi: 10.1021/acsami.3c07547. Epub 2023 Oct 31.
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) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced / 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 O 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.
最近的研究表明，线粒体功能障碍和DNA损伤对细胞存活有至关重要的影响，这被认为是癌症治疗的治疗靶点之一。在本研究中，我们展示了多酚碳量子点（CQDs）对体外和体内抗肿瘤疗效影响的比较研究。由易于获得的无毒前体（间苯三酚）合成了双发射（绿色和黄色）形状特异性多酚CQDs（G-CQDs和Y-CQDs），并与由广泛报道的前体柠檬酸和尿素衍生的圆形蓝色发射CQDs（B-CQDs）相比，研究了合成探针的抗肿瘤特性。B-CQDs具有细胞核靶向特性，而G-CQDs和Y-CQDs具有线粒体靶向特性。我们发现，含多酚的CQDs（剂量为100μg/mL）通过过量积累特异性攻击线粒体，改变代谢，抑制分支模式，破坏平衡/内稳态，并最终产生氧化应激水平，导致体外癌细胞中氧化应激诱导的细胞死亡。我们表明，G-CQDs是癌细胞中氧化应激的主要原因，因为它们能够产生足够的羟基自由基和氧自由基，电子顺磁共振光谱和对苯二甲酸测试证明了这一点。此外，CQDs的近红外吸收特性在双光子（TP）发射中表现出来，该特性被用于癌细胞的TP细胞成像且无光漂白现象。体内抗肿瘤试验进一步表明，瘤内注射G-CQDs可显著提高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的纳米诊疗剂在肿瘤治疗中具有潜在作用，从而为恶性癌症的治疗提供了一种见解。
