Abstract
Carbon nanodots (CNDs) have been studied in the field of biomedicine, such as drug delivery, bioimaging and theragnosis because of their superior biocompatibility and desirable optoelectronic properties. However, limited assessments on the biological effects of CNDs, particularly the effect on oxidative stress and toxicity in living cells, are not adequately addressed. In this work, a type of nitrogen, sulfur-doped carbon nanodots (N,S-CNDs), which were found to have strong antioxidant capacity in free radical scavenging in physicochemical conditions, was investigated through measuring the fluctuations of the intracellular reactive oxygen species (ROS), such as the hydrogen peroxide and superoxide anion, at different dose exposure in two types of cell lines, EA.hy926 and A549 cells. Instead of showing antioxidative capacity, the results indicate the uptake of the N,S-CNDs induces the production of intracellular ROS, thus causing oxidative stress and deleteriousness to both cell lines. The mitochondrial membrane potential of the cells was monitored upon the N,S-CNDs treatment and found to increase monotonically with the concentration of the CNDs. In addition, the confocal imaging of the cells confirms the localization of the CNDs at the mitochondria. More evidence suggests that the N,S-CNDs may stimulate ROS generation by interacting with the electron transport chain in the mitochondrial membrane due to the sulfur composite in the CNDs.
Similar content being viewed by others
References
Zrazhevskiy P, Sena M, Gao X (2010) Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chem Soc Rev 39:4326–4354
Thomas CR, Ferris DP, Lee J-H et al (2010) Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. J Am Chem Soc 132:10623–10625
Wolfbeis OS (2015) An overview of nanoparticles commonly used in fluorescent bioimaging. Chem Soc Rev 44:4743–4768
Sun T, Zhang YS, Pang B, Hyun DC, Yang M, Xia Y (2014) Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed 53:12320–12364
Panwar N, Soehartono AM, Chan KK et al (2019) Nanocarbons for biology and medicine: sensing, imaging, and drug delivery. Chem Rev 119:9559–9656
Zhang D, Ye Z, Wei L, Luo H, Xiao L (2019) Cell membrane-coated porphyrin metal–organic frameworks for cancer cell targeting and o2-evolving photodynamic therapy. ACS Appl Mater Interfaces 11:39594–39602
Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49
Manna SK, Sarkar S, Barr J et al (2005) Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-κb in human keratinocytes. Nano Lett 5:1676–1684
Monteiro-Riviere NA, Inman AO (2006) Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 44:1070–1078
Park MVDZ, Neigh AM, Vermeulen JP et al (2011) The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials 32:9810–9817
Chong Y, Ge C, Yang Z et al (2015) Reduced cytotoxicity of graphene nanosheets mediated by blood-protein coating. ACS Nano 9:5713–5724
Soenen SJ, Parak WJ, Rejman J, Manshian B (2015) (Intra)cellular stability of inorganic nanoparticles: effects on cytotoxicity, particle functionality, and biomedical applications. Chem Rev 115:2109–2135
Wick P, Manser P, Limbach LK et al (2007) The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 168:121–131
Cui W, Li J, Zhang Y, Rong H, Lu W, Jiang L (2012) Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. Nanomedicine 8:46–53
Zhang J, Yu S-H (2016) Carbon dots: large-scale synthesis, sensing and bioimaging. Mater Today 19:382–393
Ge L, Pan N, Jin J et al (2018) Systematic comparison of carbon dots from different preparations—consistent optical properties and photoinduced redox characteristics in visible spectrum and structural and mechanistic implications. J Phys Chem C 122:21667–21676
Xu X, Ray R, Gu Y et al (2004) Electrophoretic analysis and purification of fluorescent single-walled carbon nanotube fragments. J Am Chem Soc 126:12736–12737
Mintz KJ, Zhou Y, Leblanc RM (2019) Recent development of carbon quantum dots regarding their optical properties, photoluminescence mechanism, and core structure. Nanoscale 11:4634–4652
Wang Y, Hu A (2014) Carbon quantum dots: synthesis, properties and applications. J Mater Chem C 2:6921–6939
Li H, Kang Z, Liu Y, Lee S-T (2012) Carbon nanodots: synthesis, properties and applications. J Mater Chem 22:24230–24253
Xiao L, Sun H (2018) Novel properties and applications of carbon nanodots. Nanosc Horiz 3:565–597
Wang Q, Huang X, Long Y et al (2013) Hollow luminescent carbon dots for drug delivery. Carbon 59:192–199
Das R, Bandyopadhyay R, Pramanik P (2018) Carbon quantum dots from natural resource: a review. Mater Today Chem 8:96–109
Zhang W, Chavez J, Zeng Z et al (2018) Antioxidant capacity of nitrogen and sulfur codoped carbon nanodots. ACS Appl Nano Mater 1:2699–2708
Zhang W, Zeng Z, Wei J (2017) Electrochemical study of dpph radical scavenging for evaluating the antioxidant capacity of carbon nanodots. J Phys Chem C 121:18635–18642
Ji Z, Sheardy A, Zeng Z et al (2019) Tuning the functional groups on carbon nanodots and antioxidant studies. Molecules 24:152
Das B, Pal P, Dadhich P, Dutta J, Dhara S (2019) In vivo cell tracking, reactive oxygen species scavenging, and antioxidative gene down regulation by long-term exposure of biomass-derived carbon dots. ACS Biomater Sci Eng 5:346–356
Das B, Dadhich P, Pal P, Srivas PK, Bankoti K, Dhara S (2014) Carbon nanodots from date molasses: new nanolights for the in vitro scavenging of reactive oxygen species. J Mater Chem B 2:6839–6847
Wei X, Li L, Liu J et al (2019) Green synthesis of fluorescent carbon dots from gynostemma for bioimaging and antioxidant in zebrafish. ACS Appl Mater Interfaces 11:9832–9840
Wang L, Li B, Li L et al (2017) Ultrahigh-yield synthesis of n-doped carbon nanodots that down-regulate ROS in zebrafish. J Mater Chem B 5:7848–7860
Durantie E, Barosova H, Drasler B et al (2018) Carbon nanodots: opportunities and limitations to study their biodistribution at the human lung epithelial tissue barrier. Biointerphases 13:06D404
Christensen IL, Sun Y-P, Juzenas P (2011) Carbon dots as antioxidants and prooxidants. J Biomed Nanotechnol 7:667–676
Chong Y, Ge C, Fang G et al (2016) Crossover between anti- and pro-oxidant activities of graphene quantum dots in the absence or presence of light. ACS Nano 10:8690–8699
Chen J, Dou R, Yang Z et al (2016) The effect and fate of water-soluble carbon nanodots in maize (Zea mays l.). Nanotoxicology 10:818–828
Havrdova M, Hola K, Skopalik J et al (2016) Toxicity of carbon dots—effect of surface functionalization on the cell viability, reactive oxygen species generation and cell cycle. Carbon 99:238–248
Xu Z-Q, Lan J-Y, Jin J-C, Dong P, Jiang F-L, Liu Y (2015) Highly photoluminescent nitrogen-doped carbon nanodots and their protective effects against oxidative stress on cells. ACS Appl Mater Interfaces 7:28346–28352
Nie H, Li M, Li Q et al (2014) Carbon dots with continuously tunable full-color emission and their application in ratiometric pH sensing. Chem Mater 26:3104–3112
Zhang B-X, Gao H, Li X-L (2014) Synthesis and optical properties of nitrogen and sulfur co-doped graphene quantum dots. New J Chem 38:4615–4621
Deng Y, Zhao D, Chen X, Wang F, Song H, Shen D (2013) Long lifetime pure organic phosphorescence based on water soluble carbon dots. Chem Commun 49:5751–5753
Dong Y, Pang H, Yang HB et al (2013) Carbon-based dots co-doped with nitrogen and sulfur for high quantum yield and excitation-independent emission. Angew Chem Int Ed 52:7800–7804
Zeng Z, Zhang W, Arvapalli DM et al (2017) A fluorescence-electrochemical study of carbon nanodots (CNDs) in bio- and photoelectronic applications and energy gap investigation. Phys Chem Chem Phys 19:20101–20109
van Meerloo J, Kaspers GJL, Cloos J (2011) In: Cree IA (ed) Cancer cell culture: methods and protocols. Humana Press, Totowa
Nel A, Xia T, Maedler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627
Zuberek M, Grzelak A (2018) In: Saquib Q, Faisal M, Al-Khedhairy AA, Alatar AA (eds) Cellular and molecular toxicology of nanoparticles. Springer, Cham
McCord JM (2000) The evolution of free radicals and oxidative stress. Am J Med 108:652–659
Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762
Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453–R462
Sena LA, Chandel NS (2012) Physiological roles of mitochondrial reactive oxygen species. Mol Cell 48:158–167
Reczek CR, Chandel NS (2015) Ros-dependent signal transduction. Curr Opin Cell Biol 33:8–13
Beckman K, Ames B (1998) The free radical theory of aging matures. Physiol Rev 78:547–581
Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247
Haigis MC, Yankner BA (2010) The aging stress response. Mol Cell 40:333–344
Fukumura H, Sato M, Kezuka K et al (2012) Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells. J Physiol Sci 62:251–257
Chen Q, Wang Q, Zhu J, Xiao Q, Zhang L (2018) Reactive oxygen species: key regulators in vascular health and diseases. Br J Pharmacol 175:1279–1292
Valentine JS, Wertz DL, Lyons TJ, Liou L-L, Goto JJ, Gralla EB (1998) The dark side of dioxygen biochemistry. Curr Opin Chem Biol 2:253–262
Halliwell B (1991) Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 91:S14–S22
Li X, Fang P, Mai J, Choi ET, Wang H, Yang X-f (2013) Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol 6:19
Brand MD (2016) Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic Biol Med 100:14–31
Madamanchi Nageswara R, Runge Marschall S (2007) Mitochondrial dysfunction in atherosclerosis. Circ Res 100:460–473
Suski J, Lebiedzinska M, Bonora M, Pinton P, Duszynski J, Wieckowski MR (2018) In: Palmeira CM, Moreno AJ (eds) Mitochondrial bioenergetics: methods and protocols. Springer, New York
Hua X-W, Bao Y-W, Chen Z, Wu F-G (2017) Carbon quantum dots with intrinsic mitochondrial targeting ability for mitochondria-based theranostics. Nanoscale 9:10948–10960
Gao G, Jiang Y-W, Yang J, Wu F-G (2017) Mitochondria-targetable carbon quantum dots for differentiating cancerous cells from normal cells. Nanoscale 9:18368–18378
Cao L, Wang X, Meziani MJ et al (2007) Carbon dots for multiphoton bioimaging. J Am Chem Soc 129:11318–11319
Zhang D, Wei L, Zhong M, Xiao L, Li H-W, Wang J (2018) The morphology and surface charge-dependent cellular uptake efficiency of upconversion nanostructures revealed by single-particle optical microscopy. Chemical Science 9:5260–5269
Fleischauer AT, Arab L (2001) Garlic and cancer: a critical review of the epidemiologic literature. J Nutr 131:1032S–1040S
Xu Z, Qiu Z, Liu Q et al (2018) Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections. Nat Commun 9:3713
Packer L, Suzuki YJ (1993) Vitamin e and alpha-lipoate: role in antioxidant recycling and activation of the nf-κb transcription factor. Mol Aspects Med 14:229–239
Zhang L, Niu J, Li M, Xia Z (2014) Catalytic mechanisms of sulfur-doped graphene as efficient oxygen reduction reaction catalysts for fuel cells. J Phys Chem C 118:3545–3553
Goncalves RLS, Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Brand MD (2015) Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise. J Biol Chem 290:209–227
Weiss MJ, Wong JR, Ha CS et al (1987) Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation. Proc Natl Acad Sci USA 84:5444–5448
Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ros release. Physiol Rev 94:909–950
Acknowledgements
The authors acknowledge the support of US NSF (No. 1832134). This work was performed at the JSNN, a member of South Eastern Nanotechnology Infrastructure Corridor (SENIC) and National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation (ECCS-1542174).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No potential conflict of interest was reported by the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ji, Z., Arvapalli, D.M., Zhang, W. et al. Nitrogen and sulfur co-doped carbon nanodots in living EA.hy926 and A549 cells: oxidative stress effect and mitochondria targeting. J Mater Sci 55, 6093–6104 (2020). https://doi.org/10.1007/s10853-020-04419-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10853-020-04419-7