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PEG-conjugated single-walled carbon nanotubes enhance the cellular uptake of Coenzyme Q10: in vitro evaluation and mechanism study

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Abstract

Coenzyme Q10 (CoQ10) has a wide range of physiological functions and therapeutic value. However, its biomedical application as a health product or drug is limited by its insolubility and low bioavailability. Single-walled carbon nanotubes (SWCNTs) have attracted great interest for drug or therapeutic agent delivery due to their unique properties. In this study, the pristine SWCNTs are purified with different oxidizing acid, and the resulting shortened CNTs (CNTs-COOH) are conjugated with poly-(ethylene glycol) (PEG) groups. Afterwards, CoQ10 is loaded by CNTs carriers. CNTs carriers are systematically characterized and evaluated in terms of drug loading, in vitro release, cytotoxicity, and cellular uptake. The results reveal that the sizes (length) of CNTs-COOH and CNTs-PEG are 253.2 and 328.7 nm, respectively, and they have high loading capacity for CoQ10 and low cytotoxicity toward Caco-2 cells. In comparison with CNTs-COOH, CNTs-PEG exhibited better sustained-release property for CoQ10. Also, CNTs-PEG carriers loaded with CoQ10 can be effectively delivered into cells and have enhanced cellular uptake efficiency over time. Further study results of the uptake mechanism illustrate that CNTs-PEG can be internalized into cells through the broader and more efficient entry routes, including direct penetration, clathrin-mediated endocytosis and macropinocytosis pathway. In summary, the PEG-conjugated CNTs may be used as novel nanocarriers, and the findings will contribute to the rational design of multifunctional delivery vehicles for CoQ10.

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References

  • Ali-Boucetta H, Kostarelos K (2013) Pharmacology of carbon nanotubes: toxicokinetics, excretion and tissue accumulation. Adv Drug Deliv Rev 65:2111–2119

    Article  CAS  Google Scholar 

  • Alkholy UM, Abdalmonem N, Zaki A, Elkoumi MA, Hashim MIA, Basset MAA, Salah HE (2019) The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes. J Pediatr 95:224–230

    Article  Google Scholar 

  • Bates K, Kostarelos K (2013) Carbon nanotubes as vectors for gene therapy: past achievements, present challenges and future goals. Adv Drug Deliv Rev 65:2023–2033

    Article  CAS  Google Scholar 

  • Beg S, Javed S, Kohli K (2010) Bioavailability enhancement of coenzyme Q10: an extensive review of patents. Recent Pat Drug Deliv Formul 4:245–255

    Article  CAS  Google Scholar 

  • Bhattacharya K, Andon FT, El-Sayed R, Fadeel B (2013) Mechanisms of carbon nanotube-induced toxicity: focus on pulmonary inflammation. Adv Drug Deliv Rev 65:2087–2097

    Article  CAS  Google Scholar 

  • Bottini M, Rosato N, Bottini N (2011) PEG-modified carbon nanotubes in biomedicine: current status and challenges ahead. Biomacromolecules. 12:3381–3393

    Article  CAS  Google Scholar 

  • Chai GH, Xu Y, Chen SQ, Cheng B, Hu FQ, You J, du YZ, Yuan H (2016) Transport mechanisms of solid lipid nanoparticles across Caco-2 cell monolayers and their related cytotoxicology. ACS Appl Mater Interfaces 8:5929–5940

    Article  CAS  Google Scholar 

  • Costa PM, Bourgognon M, Wang JT, Al-Jamal KT (2016) Functionalised carbon nanotubes: From intracellular uptake and cell-related toxicity to systemic brain delivery. J Control Release 241:200–219

    Article  CAS  Google Scholar 

  • Donkor DA, Tang XS (2014) Tube length and cell type-dependent cellular responses to ultra-short single-walled carbon nanotube. Biomaterials. 35:3121–3131

    Article  CAS  Google Scholar 

  • Gong H, Peng R, Liu Z (2013) Carbon nanotubes for biomedical imaging: the recent advances. Adv Drug Deliv Rev 65:1951–1963

    Article  CAS  Google Scholar 

  • Hao Y, Yang X, Shi Y, Xing J, Marowitch J, Chen J, Chen J (2012) FITC delivery into plant cells using magnetic single-walled carbon nanotubes. J Nanosci Nanotechnol 12:6287–6293

    Article  CAS  Google Scholar 

  • Hargreaves IP (2014) Coenzyme Q10 as a therapy for mitochondrial disease. Int J Biochem Cell Biol 49:105–111

    Article  CAS  Google Scholar 

  • Hargreaves IP, Mantle D (2019a) Coenzyme Q10 supplementation in fibrosis and aging. Adv Exp Med Biol 1178:103–112

    Article  CAS  Google Scholar 

  • Hargreaves IP, Mantle D (2019b) Supplementation with selenium and coenzyme Q10 in critically ill patients. Br J Hosp Med (Lond) 80:589–593

    Article  CAS  Google Scholar 

  • Karchemski F, Zucker D, Barenholz Y, Regev O (2012) Carbon nanotubes-liposomes conjugate as a platform for drug delivery into cells. J Control Release 160:339–345

    Article  CAS  Google Scholar 

  • Karimi M, Solati N, Ghasemi A, Estiar MA, Hashemkhani M, Kiani P, Mohamed E, Saeidi A, Taheri M, Avci P, Aref AR, Amiri M, Baniasadi F, Hamblin MR (2015) Carbon nanotubes part II: a remarkable carrier for drug and gene delivery. Expert Opin Drug Deliv 12:1089–1105

    Article  CAS  Google Scholar 

  • Khattab A, Hassanin L, Zaki N (2017) Self-nanoemulsifying drug delivery system of coenzyme (Q10) with improved dissolution, bioavailability, and protective efficiency on liver fibrosis. AAPS PharmSciTech 18:1657–1672

    Article  CAS  Google Scholar 

  • Kumar S, Rani R, Dilbaghi N, Tankeshwar K, Kim KH (2017) Carbon nanotubes: a novel material for multifaceted applications in human healthcare. Chem Soc Rev 46:158–196

    Article  CAS  Google Scholar 

  • Kumar S, Rao R, Kumar A, Mahant S, Nanda S (2016) Novel carriers for coenzyme Q10 delivery. Curr Drug Deliv 13:1184–1204

    Article  CAS  Google Scholar 

  • Lee PC, Chiou YC, Wong JM, Peng CL, Shieh MJ (2013) Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody. Biomaterials. 34:8756–8765

    Article  CAS  Google Scholar 

  • Li Z, de Barros ALB, Soares DCF, Moss SN, Alisaraie L (2017) Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery. Int J Pharm 524:41–54

    Article  CAS  Google Scholar 

  • Liu HT, Huang YC, Cheng SB, Huang YT, Lin PT (2016) Effects of coenzyme Q10 supplementation on antioxidant capacity and inflammation in hepatocellular carcinoma patients after surgery: a randomized, placebo-controlled trial. Nutr J 15:85

    Article  Google Scholar 

  • López-Lluch G, Del Pozo-Cruz J, Sánchez-Cuesta A, Cortés-Rodríguez AB, Navas P (2019) Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization. Nutrition. 57:133–140

    Article  Google Scholar 

  • Mao H, Kawazoe N, Chen G (2013) Uptake and intracellular distribution of collagen-functionalized single-walled carbon nanotubes. Biomaterials. 34:2472–2479

    Article  CAS  Google Scholar 

  • Markley HG (2012) CoEnzyme Q10 and riboflavin: the mitochondrial connection. Headache. 52(Suppl 2):81–87

    Article  Google Scholar 

  • Mehra NK, Jain K, Jain NK (2015) Pharmaceutical and biomedical applications of surface engineered carbon nanotubes. Drug Discov Today 20:750–759

    Article  CAS  Google Scholar 

  • Mishra V, Kesharwani P, Jain NK (2018) Biomedical applications and toxicological aspects of functionalized carbon nanotubes. Crit Rev Ther Drug Carrier Syst 35:293–330

    Article  Google Scholar 

  • Mohammadi M, Salmasi Z, Hashemi M, Mosaffa F, Abnous K, Ramezani M (2015) Single-walled carbon nanotubes functionalized with aptamer and piperazine-polyethylenimine derivative for targeted siRNA delivery into breast cancer cells. Int J Pharm 485:50–60

    Article  CAS  Google Scholar 

  • Prakash S, Malhotra M, Shao W, Tomaro-Duchesneau C, Abbasi S (2011) Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv Drug Deliv Rev 63:1340–1351

    Article  CAS  Google Scholar 

  • Ross SM (2007) Coenzyme q10: ubiquinone: a potent antioxidant and key energy facilitator for the heart. Holist Nurs Pract 21:213–214

    Article  Google Scholar 

  • Tafazoli A (2017) Coenzyme Q10 in breast cancer care. Future Oncol 13:1035–1041

    Article  CAS  Google Scholar 

  • Taghavi S, HashemNia A, Mosaffa F, Askarian S, Abnous K, Ramezani M (2016) Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells. Colloids Surf B: Biointerfaces 140:28–39

    Article  CAS  Google Scholar 

  • Takahashi M, Takahashi K (2019) Water-soluble CoQ10 as a promising anti-aging agent for neurological dysfunction in brain mitochondria. Antioxidants (Basel) 8

  • Wong BS, Yoong SL, Jagusiak A, Panczyk T, Ho HK, Ang WH, Pastorin G (2013) Carbon nanotubes for delivery of small molecule drugs. Adv Drug Deliv Rev 65:1964–2015

    Article  CAS  Google Scholar 

  • Wu H, Shi H, Zhang H, Wang X, Yang Y, Yu C, Hao C, du J, Hu H, Yang S (2014) Prostate stem cell antigen antibody-conjugated multiwalled carbon nanotubes for targeted ultrasound imaging and drug delivery. Biomaterials. 35:5369–5380

    Article  CAS  Google Scholar 

  • Yang S, Song S, Han K, Wu X, Chen L, Hu Y, Wang J, Liu B (2019) Characterization, in vitro evaluation and comparative study on the cellular internalization of mesoporous silica nanoparticle-supported lipid bilayers. Microporous Mesoporous Mater 284:212–224

    Article  CAS  Google Scholar 

  • Yang S, Wang X, Jia J, Li P (2016) Release property study on the novel divalproex sodium enteric-coated capsules. Saudi Pharm J 24:245–249

    Article  CAS  Google Scholar 

  • Zhu M, Nie G, Meng H, Xia T, Nel A, Zhao Y (2013) Physicochemical properties determine nanomaterial cellular uptake, transport, and fate. Acc Chem Res 46:622–631

    Article  CAS  Google Scholar 

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Acknowledgements

This work was financially supported by the Foundation for University Key Teacher by Henan University of Technology (No. 21420075), the National Key Research and Development Plan (No. 2016YFD0400200), the Natural Science Research Program of the Education Department of Henan Province (21A350003), the Key R&D and Promotion projects of Henan Province (Scientific and technological research project, No. 192102310419), and Natural Science Project of Zhengzhou Science and Technology Bureau (No. 20150507).

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Authors and Affiliations

  1. College of Bioengineering, Henan University of Technology, Lianhua Street, Gaoxin District, Zhengzhou, 450001, People’s Republic of China

    Shuoye Yang, Yakun Niu, Luheng Li, Jiaxin Liu, Mengjin Ma, Xiaoyu Duan, Lu Zhang, Le Wang & Lingbo Qu

  2. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, People’s Republic of China

    Lingbo Qu

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  1. Shuoye Yang
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  2. Yakun Niu
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  3. Luheng Li
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  4. Jiaxin Liu
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  7. Lu Zhang
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  8. Le Wang
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  9. Lingbo Qu
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Correspondence to Shuoye Yang or Lingbo Qu.

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Yang, S., Niu, Y., Li, L. et al. PEG-conjugated single-walled carbon nanotubes enhance the cellular uptake of Coenzyme Q10: in vitro evaluation and mechanism study. J Nanopart Res 23, 114 (2021). https://doi.org/10.1007/s11051-021-05214-4

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