Polyphenolic Carbon Quantum Dots with Intrinsic Reactive Oxygen Species Amplification for Two-Photon Bioimaging and In Vivo Tumor Therapy

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

doi:10.1021/acsami.3c07547

Polyphenolic Carbon Quantum Dots with Intrinsic Reactive Oxygen Species Amplification for Two-Photon Bioimaging and In Vivo Tumor Therapy

ACS Appl Mater Interfaces. 2023 Oct 31. doi: 10.1021/acsami.3c07547. Online ahead of print.

Authors

Sayan Deb Dutta^{1

2}, Md Moniruzzaman³, Jin Hexiu⁴, Sourav Sarkar⁵, Keya Ganguly¹, Dinesh K Patel⁶, Jagannath Mondal⁷, Yong-Kyu Lee⁷, Rumi Acharya⁸, Jongsung Kim³, Ki-Taek Lim^{1

8}

Affiliations

¹ Department of Biosystems Engineering, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea.
² Institute of Forest Science, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea.
³ Department of Chemical and Biological Engineering, Gachon University, Seongnam, Gyeonggi-do 1342, Republic of Korea.
⁴ Department of Plastic and Traumatic Surgery, Capital Medical University, Fengtai, Beijing 100069, China.
⁵ Department of Chemistry, Pohang University of Science and Technology, Pohang, Gyungbuk 37673, Republic of Korea.
⁶ School of Chemical Engineering, Yeungnam University, 280-Daehak-ro, Gyeongsan 38541, Republic of Korea.
⁷ Department of Green Bioengineering, Korea National University of Transportation, Chungju 27470, Republic of Korea.
⁸ Interdisciplinary Program in Smart Agriculture, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea.

PMID: 37905899
DOI: 10.1021/acsami.3c07547

Abstract

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.

Keywords: mitochondrial dysfunctions; nanotheranostics; oxidative stress; polyphenolic CQDs; two-photon imaging.