Skip to main content

Advertisement

SpringerLink
Log in

Multi-functionalized single-walled carbon nanotubes as delivery carriers: promote the targeting uptake and antitumor efficacy of doxorubicin

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

As one of carbon-based nanomaterials, single-walled carbon nanotubes (SWCNTs) are widely regarded as potentially potent drug delivery carriers on account of their prominent properties. Nevertheless, their biomedical application, particularly in the drug delivery field has been seriously restricted by some inherent defects. In this study, SWCNTs materials were functionalized by covalent and non-covalent approaches, respectively. In short, the pristine SWCNTs were first purified with strong oxidizing acids (H2SO4/HNO3), and the resulting carboxylated ones (CNTs) were attached sequentially by different modification agents, including polyethylene glycol (PEG), polyethyleneimine (PEI), folic acid (FA) and chitosan (CS). Various nanocarriers were then systematically characterized and comparatively evaluated. The results illustrated that all CNTs samples could act as drug delivery carriers since they had high drug loading efficiency, good biocompatibility and responsive drug release. In comparison with other CNTs, multi-functionalized ones (CNTs-PPFC) exhibited more excellent performance, such as rapid drug release at low pH condition, higher cell internalization efficiency, and enhanced antitumor activity toward MCF-7 cells. These advantages should be attributed to their better dispersion state and comparably higher affinity with tumor cells, which favor the more efficient selective cellular uptake and subsequent drug accumulation. Moreover, further pharmacological mechanism analysis also revealed that CNTs-PPFC/DOX could induce the apoptosis of MCF-7 cells most effectively, by triggering ROS overproduction and affecting cell cycle distribution. In conclusion, the multi-functionalized CNTs-PPFC can be utilized as promising nanocarriers, and the findings will contribute to the rational design of novel delivery vehicles for anticancer drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig.4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Germain, M., Caputo, F., Metcalfe, S., et al.: Delivering the power of nanomedicine to patients today. J. Control Release. 326, 164–171 (2020)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Lee, J.H., Luo, J., Choi, H.K., Chueng, S.D., Lee, K.B., Choi, J.W.: Functional nanoarrays for investigating stem cell fate and function. Nanoscale. 12, 9306–9326 (2020)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Wagner, V., Dullaart, A., Bock, A.K., Zweck, A.: The emerging nanomedicine landscape. Nat. Biotechnol. 24, 1211–1217 (2006)

    Article  PubMed  CAS  Google Scholar 

  4. Xiao, S., Chen, L.: The emerging landscape of nanotheranostic-based diagnosis and therapy for osteoarthritis. J. Control Release. 328, 817–833 (2020)

    Article  PubMed  CAS  Google Scholar 

  5. Chauhan, V.P., Jain, R.K.: Strategies for advancing cancer nanomedicine. Nat. Mater. 12, 958–962 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Shi, J., Kantoff, P.W., Wooster, R., Farokhzad, O.C.: Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer. 17, 20–37 (2017)

    Article  PubMed  CAS  Google Scholar 

  7. Guo, P., Huang, J., Moses, M.A.: Cancer Nanomedicines in an Evolving Oncology Landscape. Trends Pharmacol. Sci. 41, 730–742 (2020)

    Article  PubMed  CAS  Google Scholar 

  8. Davoodi, P., Lee, L.Y., Xu, Q., et al.: Drug delivery systems for programmed and on-demand release. Adv. Drug Deliv Rev. 132, 104–138 (2018)

    Article  PubMed  CAS  Google Scholar 

  9. Blanco, E., Shen, H., Ferrari, M.: Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Sun, Q., Zhou, Z., Qiu, N., Shen, Y.: Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization.Adv Mater. ; 29. (2017)

  11. Li, Z., de Barros, A.L.B., Soares, D.C.F., Moss, S.N., Alisaraie, L.: Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery. Int. J. Pharm. 524, 41–54 (2017)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Wong, B.S., Yoong, S.L., Jagusiak, A., et al.: Carbon nanotubes for delivery of small molecule drugs. Adv. Drug Deliv Rev. 65, 1964–2015 (2013)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Lanone, S., Andujar, P., Kermanizadeh, A., Boczkowski, J.: Determinants of carbon nanotube toxicity. Adv. Drug Deliv Rev. 65, 2063–2069 (2013)

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Rode, A., Sharma, S., Mishra, D.K.: Carbon Nanotubes: Classification, Method of Preparation and Pharmaceutical Application. Curr. Drug Deliv. 15, 620–629 (2018)

    Article  PubMed  CAS  Google Scholar 

  19. Vardharajula, S., Ali, S.Z., Tiwari, P.M., et al.: Functionalized carbon nanotubes: biomedical applications. Int. J. Nanomedicine. 7, 5361–5374 (2012)

    PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Karimi, M., Solati, N., Amiri, M., et al.: Carbon nanotubes part I: preparation of a novel and versatile drug-delivery vehicle. Expert Opin. Drug Deliv. 12, 1071–1087 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Karimi, M., Solati, N., Ghasemi, A., et al.: Carbon nanotubes part II: a remarkable carrier for drug and gene delivery. Expert Opin. Drug Deliv. 12, 1089–1105 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Mehra, N.K., Palakurthi, S.: Interactions between carbon nanotubes and bioactives: a drug delivery perspective. Drug Discov Today. 21, 585–597 (2016)

    Article  PubMed  CAS  Google Scholar 

  25. Mody, N., Tekade, R.K., Mehra, N.K., Chopdey, P., Jain, N.K.: Dendrimer, liposomes, carbon nanotubes and PLGA nanoparticles: one platform assessment of drug delivery potential. AAPS PharmSciTech. 15, 388–399 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  30. Shariatinia, Z.: Carboxymethyl chitosan: Properties and biomedical applications. Int. J. Biol. Macromol. 120, 1406–1419 (2018)

    Article  PubMed  CAS  Google Scholar 

  31. Zhang, E., Xing, R., Liu, S., Qin, Y., Li, K., Li, P.: Advances in chitosan-based nanoparticles for oncotherapy. Carbohydr. Polym. 222, 115004 (2019)

    Article  PubMed  CAS  Google Scholar 

  32. Arola, O.J., Saraste, A., Pulkki, K., Kallajoki, M., Parvinen, M., Voipio-Pulkki, L.M.: Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res. 60, 1789–1792 (2000)

    PubMed  CAS  Google Scholar 

  33. Donkor, D.A., Tang, X.S.: Tube length and cell type-dependent cellular responses to ultra-short single-walled carbon nanotube. Biomaterials. 35, 3121–3131 (2014)

    Article  PubMed  CAS  Google Scholar 

  34. Yang, S., Wang, Z., Ping, Y., et al.: PEG/PEI-functionalized single-walled carbon nanotubes as delivery carriers for doxorubicin: synthesis, characterization, and in vitro evaluation. Beilstein J. Nanotechnol. 11, 1728–1741 (2020)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Khatti, Z., Hashemianzadeh, S.M.: Investigation of thermodynamic and structural properties of drug delivery system based on carbon nanotubes as a carboplatin drug carrier by molecular dynamics simulations. J. Incl. Phenom. Macrocycl. Chem. 83, 131–140 (2015)

    Article  CAS  Google Scholar 

  36. Mahdavifar Z, Moridzadeh R. Theoretical prediction of encapsulation and adsorption of platinum-anticancer drugs into single walled boron nitride and carbon nanotubes. J Incl Phenom Macrocycl Chem. 2014;79, 443–57.

  37. Shahabi M, Raissi H. Investigation of the solvent effect, molecular structure, electronic properties and adsorption mechanism of Tegafur anticancer drug on Graphene nanosheet surface as drug delivery system by molecular dynamics simulation and density functional approach. J Incl Phenom Macrocycl Chem. 2017; 88, 159–69.

  38. Zhao Y, Zhao T, Cao Y, et al. Temperature-Sensitive Lipid-Coated Carbon Nanotubes for Synergistic Photothermal Therapy and Gene Therapy. J Acs Nano. 2021; 15: 6517-29.

  39. Wang D, Zhang N, Jing X, et al. A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy. Journal of Materials Chemistry B. 2020; 8: 8271-81.

  40. Mohammadi, M., Salmasi, Z., Hashemi, M., Mosaffa, F., Abnous, K., Ramezani, M.: 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 (2015)

    Article  PubMed  CAS  Google Scholar 

  41. Liu, C., Yuan, J., Luo, X., et al.: Folate-Decorated and Reduction-Sensitive Micelles Assembled fromAmphiphilic Polymer – Camptothecin Conjugates for IntracellularDrug Delivery. Mol. Pharmaceut. 11, 4258–4242 (2014)

    Article  CAS  Google Scholar 

  42. Wen, L., Ding, W., Yang, S., Xing, D.: Microwave pumped high-efficient thermoacoustic tumor therapy with single wall carbon nanotubes. Biomaterials. 75, 163–173 (2016)

    Article  PubMed  CAS  Google Scholar 

  43. Gu, J., Li, M., Wu, X., et al.: Anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines in vitro. J. Gastrointest. Surg. 17, 36–44 (2014)

    Google Scholar 

  44. Yang, S., Yang, Y., Yang, Y., et al.: Iron-Palladium Decorated Carbon Nanotubes Achieve Radiosensitization via Reactive Oxygen Species Burst. Front. Bioeng. Biotechnol. 21, 683363 (2021)

    Article  Google Scholar 

  45. Lee, P.C., Chiou, Y.C., Wong, J.M., Peng, C.L., Shieh, M.J.: Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody. Biomaterials. 34, 8756–8765 (2013)

    Article  PubMed  CAS  Google Scholar 

  46. Miao, Y., Zhang, H., Pan, Y., et al.: Single-walled carbon nanotube: One specific inhibitor of cancer stem cells in osteosarcoma upon downregulation of the TGFbeta1 signaling. Biomaterials. 149, 29–40 (2017)

    Article  PubMed  CAS  Google Scholar 

  47. Lu, G.H., Shang, W.T., Deng, H., et al.: Targeting carbon nanotubes based on IGF-1R for photothermal therapy of orthotopic pancreatic cancer guided by optical imaging. Biomaterials. 195, 13–22 (2019)

    Article  PubMed  CAS  Google Scholar 

  48. Del Bino, G., Darzynkiewicz, Z.: Camptothecin, teniposide, or 4’-(9-acridinylamino)-3-methanesulfon-m-anisidide, but not mitoxantrone or doxorubicin, induces degradation of nuclear DNA in the S phase of HL-60 cells. Cancer Res. 51, 1165–1169 (1991)

    PubMed  Google Scholar 

  49. Mo, J., He, L., Ma, B., Chen, T.: Tailoring Particle Size of Mesoporous Silica Nanosystem To Antagonize Glioblastoma and Overcome Blood-Brain Barrier. ACS Appl. Mater. Interfaces. 8, 6811–6825 (2016)

    Article  PubMed  CAS  Google Scholar 

  50. Huang, Y., He, L., Song, Z., et al.: Phycocyanin-based nanocarrier as a new nanoplatform for efficient overcoming of cancer drug resistance. J. Mater. Chem. B. 5, 3300–3314 (2017)

    Article  PubMed  CAS  Google Scholar 

  51. He, L., Lai, H., Chen, T.: Dual-function nanosystem for synergetic cancer chemo-/radiotherapy through ROS-mediated signaling pathways. Biomaterials. 51, 30–42 (2015)

    Article  PubMed  CAS  Google Scholar 

  52. Fan, C., Chen, J., Wang, Y., et al.: Selenocystine potentiates cancer cell apoptosis induced by 5-fluorouracil by triggering reactive oxygen species-mediated DNA damage and inactivation of the ERK pathway. Free Radic Biol Med. 65, 305–316 (2013)

    Article  PubMed  CAS  Google Scholar 

  53. Salas-Treviño, D., Saucedo-Cárdenas, O., Loera-Arias, M.J., et al.: Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Filled with Carboplatin as a Novel Drug Nanocarrier against Murine Lung Cancer Cells. Nanomater. 9, 1572 (2019)

    Article  CAS  Google Scholar 

Download references

Funding

This work was financially supported by the Foundation for Key Teacher of Colleges and Universities of Henan province (No: 2020GGJS090), Cultivation Programme for Young Backbone Teachers in Henan University of Technology (No: 21420075), Natural Science Innovation Fund of Henan University of Technology (2021ZKCJ16), the Natural Science Research Program of the Education Department of Henan Province (No: 21A350003) and the National Key Research and Development Plan (No: 2016YFD0400200).

Author information

Authors and Affiliations

  1. College of Bioengineering, Henan University of Technology, Lianhua Street, Gaoxin District, 450001, Zhengzhou, P. R. China

    Shuoye Yang, Jiaxin Liu, Yahong Ping, Zhenwei Wang, Jiaying Zhang, Lu Zhang, Lan Cui & Lingbo Qu

  2. Key Laboratory of Functional Molecules for Biomedical Research, Zhengzhou, P. R. China

    Shuoye Yang, Lu Zhang & Lan Cui

  3. College of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou, P. R. China

    Yongmei Xiao

  4. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, P. R. China

    Lingbo Qu

Authors
  1. Shuoye Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiaxin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yahong Ping
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhenwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiaying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lan Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yongmei Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lingbo Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shuoye Yang or Lingbo Qu.

Ethics declarations

Conflict of interest

There are no conflicts of interest to declare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, S., Liu, J., Ping, Y. et al. Multi-functionalized single-walled carbon nanotubes as delivery carriers: promote the targeting uptake and antitumor efficacy of doxorubicin. J Incl Phenom Macrocycl Chem 102, 801–817 (2022). https://doi.org/10.1007/s10847-022-01163-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-022-01163-0

Keywords

Search

Navigation