Abstract
Gold nanoparticles (AuNPs) offer a wide range of applications in biomedicine due to their unique physicochemical properties, usually associated with their size and shape. The effects of drugs and other materials, such as nanoparticles, on mitochondrial bioenergetics can be analyzed to evaluate their toxicity. Therefore, we aimed to investigate the shape-dependent effect of AuNPs on mitochondrial bioenergetics. As a case of study, we exposed isolated rat liver mitochondria to gold nanoparticles with different shapes. Our initial results showed that the presence of the same amounts of gold nanorods (AuNRs) and nanospheres (AuNSs), resulted in similar effects of decreases in mitochondrial oxygen consumption, H2O2 levels, and swelling, even in the presence of Cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore (MPTP). However, the mitochondrial electrochemical potential could be either sustained or dissipated depending on the total surface area of the particles in the medium.
Graphical abstract
Toxicity of gold nanoparticles with different shapes on isolated mitochondria
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Abbreviations
- AuNPs:
-
Gold nanoparticles
- AuNRs:
-
Gold nanorods
- AuNSs:
-
Gold nanospheres
- BSA:
-
Bovine serum albumin
- CCCP:
-
Carbonyl cyanide chlorophenyl hydrazone
- CsA:
-
Cyclosporin A
- CTAB:
-
Hexadecyltrimethylammonium bromide
- LSPR:
-
Localized surface plasmon resonance
- MMP:
-
Mitochondrial electrochemical membrane potential
- MPTP:
-
Mitochondrial permeability transition pore
- MS:
-
Maximal state
- RLM:
-
Rat liver mitochondria
- ROS:
-
Reactive oxygen species
- PS:
-
Phosphorylation state
- SI:
-
Substrates for complex I
References
Abdoon AS, Al-Ashkar EA, Kandil OM, Shaban AM, Khaled HM, El-Sayed MA et al (2016) Efficacy and toxicity of plasmonic photothermal therapy (PPTT) using gold nanorods (GNRs) against mammary tumors in dogs and cats. Nanomedicine: Nanotechnology. Biology, and Medicine 12:2291–2297. https://doi.org/10.1016/j.nano.2016.07.005
Aldewachi H, Chalati T, Woodroofe MN, Bricklebank N, Sharrack B, Gardiner P (2017) Gold Nanoparticle-Based Colorimetric Biosensors. Nanoscale 10:18–33. https://doi.org/10.1039/c7nr06367a
Alkilany AM, Murphy CJ (2010) Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? J Nanopart Res 12:2313–2333. https://doi.org/10.1007/s11051-010-9911-8
Azevedo RDS, Falcao KVG, Amaral IPG, Leite ACR, Bezerra RS (2020) Mitochondria as targets for toxicity and metabolism research using zebrafish. Biochim Biophys Acta Gen Subj 1864:129634. https://doi.org/10.1016/j.bbagen.2020.129634
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1006/abio.1976.9999
Cai Z, Yan L (2013) Protein oxidative modifications: beneficial roles in disease and health. J Biochem Pharmacol Res 1:15–26
Chance B, Williams GR (1955) A simple and rapid assay of oxidative phosphorylation. Nature 175:1120–1121. https://doi.org/10.1038/1751120a0
Chang H, Murphy CJ (2018) Mini gold nanorods with tunable plasmonic peaks beyond 1000 nm. Chem Mater 30:1427–1435. https://doi.org/10.1021/acs.chemmater.7b05310
Chmielewska SJ, Sklodowski K, Depciuch J, Deptula P, Piktel E, Fiedoruk K, Kot P et al (2021) Bactericidal properties of rod-, peanut-, and star-shaped gold nanoparticles coated with ceragenin CSA-131 against multidrug-resistant bacterial strains. Pharmaceutics 13:425. https://doi.org/10.3390/pharmaceutics13030425
Cho EC, Au L, Zhang Q, Xia Y (2010) The effects of size, shape, and surface functional group of gold nanostructures on their adsorption and internalization by cells. Small 6:517–522. https://doi.org/10.1002/smll.200901622
Conçalves JP, Cruz AD, Nunes AM, Meneghetti MR, Barros HR, Borges BS et al (2021) Biocompatible gum arabic-gold nanorod composite as an effective theray for mistreated melanomas. Int J Biol Macromol 185:551–561. https://doi.org/10.1016/j.ijbiomac.2021.06.172
Erich G, MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun. 1:1–44. https://doi.org/10.26124/bec:2020-0001.v1
Fenger R, Fertitta E, Kirmse H, Thunemann AF, Rademann K (2012) Size dependent catalysis with CTAB-stabilized gold nanoparticles. Phys Chem Chem Phys 14:9343–9349. https://doi.org/10.1039/c2cp40792b
Fu H, Huang L, Xu C, Zhang J, Li D, Ding L et al (2019) Highly biocompatible thermosensitive nanocomposite gel for combined therapy of hepatocellular carcinoma via the enhancement of mitochondria related apoptosis. Nanomedicine: Nanotechnology, Biology, and Medicine 21:102062. https://doi.org/10.1016/j.nano.2019.102062
Gao Y, Torrente-Murciano L (2020) Mechanistic insights of the reduction of gold salts in the Turkevich protocol. Nanoscale 12:2740–2751. https://doi.org/10.1039/c9nr08877f
Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA (2010) Gold nanoparticles for biology and medicine. Angew Chem Int Ed 49:3280–3294. https://doi.org/10.1002/anie.200904359
Grzelczak M, Pérez-Juste J, Mulvaney P, Liz-Marzán LM (2008) Shape control in gold nanoparticle synthesis. Chem Soc Rev 37:1783. https://doi.org/10.1039/B711490G
Jv Y, Li B, Cao R (2010) Positively-charged gold nanoparticles as peroxidiase mimic and their application in hydrogen peroxide and glucose detection. Chem Commun 46:8017–8019. https://doi.org/10.1039/C0CC02698K
Lee KX, Shameli K, Yew YP, Jahangirian H, Rafiee-Moghaddam R, Webster TJ (2020) Recent developments in the facile bio-synthesis of gold nanoparticles (AuNPs) and their biomedical applications. Int J Nanomedicine 15:275–300. https://doi.org/10.2147/IJN.S233789
Lu F, Zhang Y, Zhang L, Zhang Y, Wang JX, Adzic RR et al (2011) Truncated ditetragonal gold prisms as nanofacet activators of catalytic platinum. J Am Chem Soc 133:18074–18077. https://doi.org/10.1021/ja207848e
Manohar N, Reynoso FJ, Diagaradjane P, Krishnan S, Cho SH (2016) Quantitative imaging of gold nanoparticle distribution in a tumor-bearing mouse using benchtop x-ray fluorescence computed tomography. Sci Rep 6:22079. https://doi.org/10.1038/srep22079
Matricardi C, Hanske C, Garcia-Pomar JL, Langer J, Mihi A, Liz-Marzán LM (2018) Gold nanoparticle plasmonic superlattices as surface-enhanced raman spectroscopy substrates. ACS Nano 12:8531–8539. https://doi.org/10.1021/acsnano.8b04073
Nunes AM, Silva KRM, Calado CMS, Saraiva KLA, Figueiredo RCB, Leite ACR et al (2019) Evaluation of gold nanorods toxicity on isolated mitochondria. Toxicology 413:24–32. https://doi.org/10.1016/j.tox.2018.12.002
Oliveira FM, Nascimento LRB, Calado CMS, Meneghetti MR, Silva MGA (2016) Aqueous-phase catalytic chemical reduction of p-nitrophenol employing soluble gold nanoparticles with different shapes. Catalysts 6:215. https://doi.org/10.3390/catal6120215
Pada A, Desai D, Sun K, Govardhanam NP, Tornquist K, Zhang J et al (2019) Comparison of polydopamine-coated mesoporous silica nanorods and spheres for the delivery of hydrophilic and hydrophobic anticancer drugs. Int J Mol Sci 20:3408. https://doi.org/10.3390/ijms20143408
Punjani K, Bhimalapuram P (2021) Study of shape changes during nanoparticle growth using kinetic Monte Carlo simulation: a case study on gold nanoparticles. J Chem Sci 133:101. https://doi.org/10.1007/s12039-021-01949-8
Singh P, Pandit S, Mokkapati VRSS, Garg A, Ravikumar V, Mijakovic I (2018) Gold nanoparticles in diagnostics and therapeutics for human cancer. Int J Mol Sci 19:1979. https://doi.org/10.3390/ijms19071979
Smith AM, Mancini MC, Nie S (2009) Second window for in vivo imaging. Nat Nanotechnol 4:710–711. https://doi.org/10.1038/nnano.2009.326
Sun T, Dou J, Liu S, Wang X, Zheng X, Wang Y, Pei J, Xie Z (2018) Second near-infrared conjugated polymer nanoparticles for photoacoustic imaging and photothermal therapy. ACS Appl Mater Interfaces 10:7919–7926. https://doi.org/10.1021/acsami.8b01458
Suski J, Lebiedzinska M, Bonora M, Pinton P, Duszynski J, Wieckowski MR (2018) “Relation between mitochondrial membrane potential and ROS formation”. Mitochondrial Bioenergetics: Methods and Protocols edited by Carlos M Palmeira and Antonio J. Moreno. Methods Mol Biol 2018:357–381. https://doi.org/10.1007/978-1-4939-7831-1
Thakuria A, Kataria B, Gupta D (2021) Nanoparticle-based methodologies for targeted drug delivery-an insight. J Nanopart Res 23:87. https://doi.org/10.1007/s11051-021-05190-9
Velho JA, Okanodo H, Degasperi GR, Matsumoto MY, Alberici LC, Cosso RG et al (2006) Statins induce calcium-dependent mitochondrial permeability transition. Toxicology 219:124–132. https://doi.org/10.1016/j.tox.2005.11.007
Vercesi AE, Bernardes CF, Hoffmann ME, Gadelha FR, Docampo R (1991) Digitonin permeabilization does not affect mitochondrial function and allows the determination of the mitochondrial membrane potential of Trypanosoma cruzi in situ. J Biol Chem 266:14431–14434. https://doi.org/10.1016/S0021-9258(18)98703-X
Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12:685–689. https://doi.org/10.1038/nrc3365
Wang X, Li Y, Wang H, Fu Q, Peng J, Wang Y et al (2010) Gold nanorod-based localized surface plasmon resonance biosensor for sensitive detection of hepatitis B virus in buffer, blood serum and plasma. Biosens Bioelectron 26:404–410. https://doi.org/10.1016/j.bios.2010.07.121
Wang L, Liu Y, Li W, Jiang X, Ji Y, Wu X et al (2011) Selective targeting of gold nanorods at the mitochondria of cancer cells: implications for cancer therapy. Nano Lett 11:772–780. https://doi.org/10.1021/nl103992v
Wang Z, Dong J, Zhao Q, Ying Y, Zhang L, Zou J, Zhao S, Wang J, Zhao Y (2020) Gold nanoparticle-mediated delivery of paclitaxel and nucleic acids for cancer therapy (Review). Mol Med Rep 22:4475–4484. https://doi.org/10.3892/mmr.2020.11580
Woźniak A, Malankowska A, Nowaczyk G, Grześkowiak BF, Tuśnio K, Słomski R et al (2017) Size and shape-dependent cytotoxicity profile of gold nanoparticles for biomedical applications. J Mater Sci Mater Med 28:92. https://doi.org/10.1007/s10856-017-5902-y
Zhang Y, Zhan X, Xiong J, Peng S, Huang W, Joshi R et al (2018) Temperature-dependent cell death patterns induced by functionalized gold nanoparticle photothermal therapy in melanoma cells. Sci Rep 8:1–9. https://doi.org/10.1038/s41598-018-26978-1
Zhou M, Diwu Z, Panchuk-Voloshina N, Haugland RP (1997) A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. Anal Biochem 253:162–168. https://doi.org/10.1006/abio.1997.2391
Acknowledgements
The authors are grateful for the support of the following Brazilian research agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Alagoas (FAPEAL), Financiadora de Estudos e Projetos (FINEP), and Instituto Nacional de Ciência e Tecnologia de Catálise em Sistemas Moleculares e Nanoestruturados (INCT-Catalise). AMN, RCSF, KRMS, and SMB acknowledge CNPq for scholarships. MRM is grateful to CNPq for a research fellowship.
Funding
This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)—Project n° 408139/2018–8.
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Abner Magalhães Nunes was responsible for conceptualization; investigation; methodology; writing—original draft; and writing—review and editing. Reginaldo Correia da Silva Filho was responsible for investigation; methodology; and writing—original draft. Kleyton Ritomar Monteiro da Silva was responsible for investigation; methodology; and writing—original draft. Sarah Morais Bezerra was responsible for investigation and methodology. Regina Célia Bressan Queiroz de Figueiredo was responsible for investigation; methodology; and writing—original draft. Karina Lidianne Alcântara Saraiva was responsible for investigation; methodology; and writing—original draft. Ana Catarina Rezende Leite was responsible for conceptualization; funding acquisition; investigation; methodology; project administration; writing—original draft; and writing—review and editing. Mario Roberto Meneghetti was responsible for conceptualization; funding acquisition; investigation; methodology; project administration; writing—original draft; and writing—review and editing.
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Highlights
• The shape-dependent toxicity and mechanism of AuNPs were studied in isolated RLM.
• AuNSs and AuNRs show a similar effect in most of the mitochondrial bioenergetic parameters.
• AuNPs can interact with the mitochondria and disrupt the electron transport chain.
• AuNRs can induce an early dissipation of the MMP.
• The MMP disruption induced by AuNRs is not related to the opening of the MPTP.
• The differences were attributed to the total surface area of the AuNPs.
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Nunes, Á.M., da Silva Filho, R.C., da Silva, K.R.M. et al. Gold nanoparticles with different shapes can cause distinct effect on mitochondria bioenergetics. J Nanopart Res 24, 31 (2022). https://doi.org/10.1007/s11051-022-05410-w
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DOI: https://doi.org/10.1007/s11051-022-05410-w