TY - JOUR

T1 - Carbon nanoparticles induce DNA repair and PARP inhibitor resistance associated with nanozyme activity in cancer cells

AU - Fan, Haiyan

AU - Sun, Qinglei

AU - Dukenbayev, Kanat

AU - Benassi, Enrico

AU - Manarbek, Limara

AU - Nurkesh, Ayan A.

AU - Khamijan, Medina

AU - Mu, Chenglin

AU - Li, Guoliang

AU - Razbekova, Madina

AU - Chen, Zhenbang

AU - Amin, Amr

AU - Xie, Yingqiu

N1 - Funding Information: This work was supported by Nazarbayev University Faculty-Development Competitive Research Grants Program with grant ID: 16392864; i.e. 15798117 (i.e.16797152;110119FD4531), and ID: 40018227; i.e. ID: 40018290 (11022021FD2920) with title” Improving the efficacy of PARP inhibition with Sulfur-Carbon Nanodots through DNA damage response” to PI Yingqiu Xie; and ID: 15874919 to PI, Haiyan Fan (i.e.110119FD4542 and 11022021FD2928) and Co-PI, Yingqiu Xie. The project is also supported by UAEU-AUA Fellowship Award to Yingqiu Xie and Amr Amin (2019; 12R118). Funding Information: We would like to thank the students including Adilet Dautov, Balnur Bazarbayeva, Nazgul Ibragimova, Shuwen Sunchen, Lulu Liu, Yan Zhang, Alibek Ysmaiyl, Aigerim Kabulova, Saltanat Kaldar, Diana Aliyeva, Aigerim Nugmanova, Ruslan Nassyrov, and Ayagoz Meirkhanova who contributed their support, assistance or valuable comments. We thank the Nazarbayev University Faculty-Development Competitive Research Grants Program with grant ID 16392864; 15798117 (i.e.16797152;110119FD4531), and ID: 40018227; i.e. 40018290 (11022021FD2920) with title” Improving the efficacy of PARP inhibition with Sulfur-Carbon Nanodots through DNA damage response” to PI Yingqiu Xie; and ID: 15874919 to PI Haiyan Fan (i.e.110119FD4542 and 11022021FD2928) and Co-PI, YX. YX and AA thank UAEU-AUA Fellowship grant support (2019; 12R118). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Background: Quantum nanodots especially carbon nanoparticles (CNPs) have been widely studied in biomedicine in imaging, and drug delivery, but anti-cancer mechanisms remain elusive. Methods: Here, we investigated a type of cell death induced by food (beet, soybean) derived CNPs in cancer cells and tested whether CNPs induced DNA damage and resistant to anti-cancer agent PARP inhibitor (PARPi) could be overcome by quantum calculations, TEM, AFM, FT-IR, soft agar assay, and cytotoxicity assay. Results: At high doses, CNPs derived from beet lead to a pop-like apoptosis (Carbopoptosis) in cancer cells. Quantum mechanical calculations confirmed CNPs binding with phosphate groups as well as DNA bases. At low doses, CNPs develop PARPi drug resistance through interactions between CNPs and PARPi. A synergistic drug effect was achieved with the combination of phosphatase inhibitor (PPi), PARPi, and CNPs. This is corroborated by the fact that sulfur modulated CNPs which exhibit super high phosphatase nanozyme activity abrogated the CNPs induced colony formation in anchorage-independent cancer cell growth. Conclusion: Thus, our data suggest the CNPs intrinsic nanozyme activity of phosphatase may crosstalk with drug resistance, which can be reversed upon modulations.

AB - Background: Quantum nanodots especially carbon nanoparticles (CNPs) have been widely studied in biomedicine in imaging, and drug delivery, but anti-cancer mechanisms remain elusive. Methods: Here, we investigated a type of cell death induced by food (beet, soybean) derived CNPs in cancer cells and tested whether CNPs induced DNA damage and resistant to anti-cancer agent PARP inhibitor (PARPi) could be overcome by quantum calculations, TEM, AFM, FT-IR, soft agar assay, and cytotoxicity assay. Results: At high doses, CNPs derived from beet lead to a pop-like apoptosis (Carbopoptosis) in cancer cells. Quantum mechanical calculations confirmed CNPs binding with phosphate groups as well as DNA bases. At low doses, CNPs develop PARPi drug resistance through interactions between CNPs and PARPi. A synergistic drug effect was achieved with the combination of phosphatase inhibitor (PPi), PARPi, and CNPs. This is corroborated by the fact that sulfur modulated CNPs which exhibit super high phosphatase nanozyme activity abrogated the CNPs induced colony formation in anchorage-independent cancer cell growth. Conclusion: Thus, our data suggest the CNPs intrinsic nanozyme activity of phosphatase may crosstalk with drug resistance, which can be reversed upon modulations.

KW - Carbon nanoparticles

KW - Carbopoptosis

KW - Drug resistance

KW - PARP inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85142716181&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/76055285-ae92-3ba0-b6b5-b6a76d1c405f/

U2 - 10.1186/s12645-022-00144-9

DO - 10.1186/s12645-022-00144-9

M3 - Article

AN - SCOPUS:85142716181

VL - 13

JO - Cancer Nanotechnology

JF - Cancer Nanotechnology

SN - 1868-6958

IS - 1

M1 - 39

ER -