A study on doxorubicin adsorption on the surface of carbon nanotube

O.V. Khora; O.V. Markitan; E.M. Demianenko; N.A. Gavryluk; V.M. Mischenko; A.G. Grebenyuk; B.M. Gorelov

doi:10.15407/hftp16.04.451

Authors

O.V. Khora Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine / Frantsevich Institute for Problems of Materials Science of National Academy of Sciences of Ukraine
O.V. Markitan Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine
E.M. Demianenko Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine / Frantsevich Institute for Problems of Materials Science of National Academy of Sciences of Ukraine
N.A. Gavryluk Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine / Frantsevich Institute for Problems of Materials Science of National Academy of Sciences of Ukraine
V.M. Mischenko “Hidrospetsefekt” Ltd
A.G. Grebenyuk Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine
B.M. Gorelov Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine

DOI:

https://doi.org/10.15407/hftp16.04.451

Keywords:

doxorubicin, carbon nanotubes, adsorption, spectrophotometry, semiempirical quantum chemical methods

Abstract

Carbon nanotubes (CNTs) are of particular interest for biomedical applications as drug transporters due to their chemical stability, biofunctionality, and biocompatibility. Currently, the issue of searching for promising adsorbents for doxorubicin (DOXO) – an antitumor cytotoxic antibiotic of the anthracycline series with a low adsorption energy value – remains relevant.

The aim of this work was to use experimental adsorption methods to determine the features of doxorubicin adsorption on the surface of carbon nanotubes, as well as spectroscopic methods to determine the structure of doxorubicin depending on the acidity of the medium. In addition to experimental research methods, to determine the features of this process at the atomic level, quantum chemistry methods were used, by means of them it is possible to obtain results of both the geometric structure of adsorption doxorubicin–CNT complexes and the energy characteristics of adsorption.

In this work, the adsorption of DOXO on the surface of carbon nanotubes was studied by spectrophotometric method as dependent on the pH of the solution and in the adsorbate concentration range of 25–250 ?M. The driving force of this adsorption process is most likely electrostatic interaction, since DOXO in the studied pH range is in the protonated form at the amino group, and the surface of nanotubes is characterized by a negative charge due to the dissociation of surface carboxyl groups. It has been found that the adsorption process proceeds by the Langmuir mechanism with a free energy of adsorption (?G₂₉₈) about 8 kJ/mol. Besides, the dependence of adsorption process on the surface charge was discovered. It was found that the adsorption process is intensified in an acidic environment.

It has been found that the enthalpy (?H₂₉₈) of the reaction of replacing water molecules with protonated DOXO is greater (-68.6 kJ/mol) than that for the similar process for the molecular form of DOXO (-47.1 kJ/mol). Quantum chemical calculations indicate that the enthalpy of DOXO adsorption on the outer surface of CNTs in aqueous solution is favorable from a thermodynamic point of view, which is in good agreement with the experimental data.

References

1. Tacar O., Sriamornsak P., Dass C.R. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J. Pharm. Pharmacol. 2013. 65(2): 157. https://doi.org/10.1111/j.2042-7158.2012.01567.x

2. Zogotto G., Gatto B., Moro S., Sissi C., Palumbo M. Anthrcyclines: recent developmentsin their separation and quantitation. J. Chromatogr. B. 2001. 764(1-2): 161. https://doi.org/10.1016/S0378-4347(01)00346-2

3. Abdullah C.S., Alam S., Aishwarya R., Miriyala S., Bhuiyan M.A.N., Panchatcharam M., Pattillo C.B., Orr A.W., Sadoshima J., Hill J.A., Md. Bhuiyan Sh. Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration. Sci. Rep. 2019. 9: 1. https://doi.org/10.1038/s41598-018-37862-3

4. Tamtaji O.R., Ardestani M.S., Taheri A.T., Hamblin M.R., Rahjoo T., Nabavizadeh F., Mirzaei H. The effects of peptide IF7-conjugated dendrimer loaded with doxorubicin on colorectal cancer. Cancer Nanotechnol. 2025. 16(11): 1. https://doi.org/10.1186/s12645-025-00316-3

5. Fornari F.A., Randolph J.K., Yalowich J.C., Ritke M.K., Gewirtz D.A. Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol. Pharmacol. 1994. 45(4): 649. https://doi.org/10.1016/S0026-895X(25)10149-1

6. Momparber R.L., Karon M., Siegel S.E., Avila F. Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res. 1976. 36(8): 2891.

7. Scheede-Bergdahl C., Jagoe R.T. After the chemotherapy: Potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood. Front. Pharmacol. 2013. 4: 1. https://doi.org/10.3389/fphar.2013.00049

8. LiechtyW.B., Kryscio D.R., Slaughter B.V., Peppas N.A. Polymers for drug delivery systems. Annu. Rev.ChemBiomol. Eng. 2010. 1: 149. https://doi.org/10.1146/annurev-chembioeng-073009-100847

9. Chi F.L., Guo Y.N., Liu J., Liu Y.L., Huo Q.H. Size-tunalbe and functional core-sheel structured silica nanoparticles for drug release. J. Phys. Chem. C. 2010. 114(6): 2519. https://doi.org/10.1021/jp910460j

10. Zgurskaya H.I., Weeks J.W., Ntreh A.T., Nickels L.M., Ewolloscheck D. Mechanism of coupling drug transport reactions located in two diferent membranes. Front. Microbiol. 2015. 6: 100. https://doi.org/10.3389/fmicb.2015.00100

11. Orozco J., Campuzano S., Kagan D., Zhou M., Gao W., Wang J. Dynamic Isolation and Unloading of Target Proteins by Aptamer-Modified Microtransporters. Anal. Chem. 2011. 83(20): 7962. https://doi.org/10.1021/ac202029k

12. Suh S., Jo A., Traore M.A., Zhan Y., Coutermarsh-Ott S., Ringel-Scaia V.M., Allen I.C., Davis R.M., Behkam B. Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine. Adv. Sci. 2018. 6: 1801309. https://doi.org/10.1002/advs.201801309

13. He H., Pham-Huy L.A., Dramou P., Xiao D., Zuo P., Pham-Huy C. Carbon Nanotubes: Applications in Pharmacy and Medicine. BioMed. Res. Int. 2013. 2738: 578290. https://doi.org/10.1155/2013/578290

14. Wu S., Zhao X., Li Y., Du Q., Sun J., Wang Y., Xia L. Adsorption Properties of Doxorubicin Hydrochloride onto Graphene Oxide: Equilibrium, Kinetic and Thermodynamic Studies. Materials. 2013. 6(5): 2026. https://doi.org/10.3390/ma6052026

15. Wu W., Wieckowski S., Pastorin G., Benincasa M., Klumpp C., Briand J.-P., Gennaro R., Prato M., Bianco A. Targeted Delivery of Amphotericin B to Cells by Using Functionalized Carbon Nanotubes. Angew. Chem. Int. Ed. Engl. 2005. 44(39): 6358. https://doi.org/10.1002/anie.200501613

16. Lam C.-W., James J.T., McCluskey R., Arepalli S., Hunter R.L. A Review of Carbon Nanotube Toxicity and Assessment of Potential Occupational and Environmental Health Risks. Crit. Rev. Toxicol. 2006. 36(3): 189. https://doi.org/10.1080/10408440600570233

17. Gannon C.J., Cherukuri P., Yakobson B.I., Cognet L., Kanzius J.S., Kittrell C., Weisman R.B., Pasquali M., Schmidt H.K., Smalley R.E., Curley S.A. Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field. Cancer. 2007. 110(12): 2654. https://doi.org/10.1002/cncr.23155

18. Panczyk T., Wolski P., Lajtar L. Coadsorption of Doxorubicin and Selected Dyes on Carbon Nanotubes. Theoretical Investigation of Potential Application as a pH-Controlled Drug Delivery System. Langmuir. 2016. 32: 4719. https://doi.org/10.1021/acs.langmuir.6b00296

19. Hao G., Xu Z.P., Li L. Manipulating extracellular tumour pH: An efective target for cancer therapy. RSC Adv. 2018. 8: 22182. https://doi.org/10.1039/C8RA02095G

20. Simon J., Flahaut E., Golzio M. Overview of carbon nanotubes for biomedical applications. Materials. 2019. 12(4): 624. https://doi.org/10.3390/ma12040624

21. Behi M., Gholami L., Naficy S., Palomba S., Dehghani F. Carbon dots: a novel platform for biomedical applications. Nanoscale Adv. 2022. 4(2): 353. https://doi.org/10.1039/D1NA00559F

22. Beg S., Rizwan M., Sheikh A.M., Hasnain M.S., Anwer K., Kohli K. Advancement in carbon nanotubes: basics, biomedical applications and toxicity. J. Pharm. Pharmacol. 2011. 63(2): 141. https://doi.org/10.1111/j.2042-7158.2010.01167.x

23. Chen Y., Mitra S. Fast Microwave-Assisted Purification, Functionalization and Dispersion of Multi-Walled Carbon Nanotubes. J. Nanosci. Nanotechnol. 2008. 8(11): 5770. https://doi.org/10.1166/jnn.2008.215

24. Chudoba D., ?udzik K., Ja?d?ewska M., Wo?oszczuk S. Kinetic and Equilibrium Studies of Doxorubicin Adsorption onto Carbon Nanotubes. Int. J. Mol. Sci. 2020. 21(21): 8230. https://doi.org/10.3390/ijms21218230

25. Wang Y., Yang S.-T., Wang Y., Liu Y., Wang H. Adsorption and desorption of doxorubicin on oxidized carbon nanotubes. Colloids Surf. B. 2012. 97: 62. https://doi.org/10.1016/j.colsurfb.2012.04.013

26. Demianenko E.M., Khora O.V., Gorelov B.M., Sementsov Yu.I., Terets M.I., Havryliuk N.A., Grebenyuk A.G., Lobanov V.V. Quantum chemical simulation of the interaction of epirubicin with a fullerene and a carbon graphene-like plane. Surface. 2023. 15(30): 34. [in Ukrainian].

27. Demianenko E.M., Khora O.V., Markitan O.V., Gavrilyuk N.A., Lobanov V.V., Gorelov B.M. Interaction of doxorubicin with carbon nanotubes. Surface. 2024. 16(31): 74. [in Ukrainian]. https://doi.org/10.15407/Surface.2024.16.074

28. Tsoneva Y., Jonker H.R.A., Wagner M., Tadjer A., Lelle M., Peneva K., Ivanova A. Molecular Structure and Pronounced Conformational Flexibility of Doxorubicin in Free and Conjugated State within a Drug-Peptide Compound. J. Phys. Chem. B. 2015. 119(7): 3001. https://doi.org/10.1021/jp509320q

29. Swietach P., Hulikova A., Patiar S., Vaughan-Jones R.D., Harris A.L. Importance of Intracellular pH in Determining the Uptake and Efficacy of the Weakly Basic Chemotherapeutic Drug, Doxorubicin. PLoS ONE. 2012. 7(4): e35949. https://doi.org/10.1371/journal.pone.0035949

30. Chudoba D., ?udzik K., Ja?d?ewska M., Wo?oszczuk S. Kinetic and Equilibrium Studies of Doxorubicin Adsorption onto Carbon Nanotubes. Int. J. Mol. Sci. 2020. 21(21): 8230. https://doi.org/10.3390/ijms21218230

31. Sinnott S.B., Andrews R. Carbon Nanotubes: Synthesis, Properties, and Applications. Crit. Rev. Solid State Mater. Sci. 2001. 26(3): 145. https://doi.org/10.1080/20014091104189

32. Santra B., Klimes J., Tkatchenko A. On the accuracy of van der Waals inclusive density-functional theory exchange-correlation functionals for ice at ambient and high pressures. J. Chem. Phys. 2013. 139(15): 154702. https://doi.org/10.1063/1.4824481

33. Stewart J.J.P. MOPAC2022. Stewart Computational Chemistry. web: HTTP://OpenMOPAC.net. 2024. (accessed on 30.01.2024, Ver. 22.1.1).

34. ?ez?? J., Hobza P. Advanced Corrections of Hydrogen Bonding and Dispersion for Semiempirical Quantum Mechanical Methods. J. Chem. Theory Comput. 2012. 8(1): 141. https://doi.org/10.1021/ct200751e

35. Klamt A., Sch??mann G. COSMO: A New Approach to Dielectric Screening in Solvents with Explicit Expressions for the Screening Energy and its Gradient. J. Chem. Soc., Perkin Trans. 2. 1993. 2(5): 799. https://doi.org/10.1039/P29930000799

36. Langmuir I. The constitution and fundamental properties of solids and liquids. J. Am. Chem. Soc. 1916. 38(11): 2221. https://doi.org/10.1021/ja02268a002

37. Freundlich H.M.F. ?ber die Adsorption in L?sungen. Z. Phys. Chem. 1906. 57: 385. https://doi.org/10.1515/zpch-1907-5723

38. Dubinin M.M., Radushkevich L.V. On the equation of the characteristic curve for active coals. Proceedings of the USSR Academy of Sciences. 1947. 55: 331.

39. Hall K.R., Eagleton L.C., Acrivos A., Vermeulen T. Pore and solid diffusion kinetics in fixed-bed adsorption under constant pattern conditions. Ind. Eng. Chem. Fundam. 1966. 5(2): 212. https://doi.org/10.1021/i160018a011

40. Tomasi J., Mennucci B., Cammi R. Quantum Mechanical Continuum Solvation Models. Chem. Rev. 2005. 105(8): 2999. https://doi.org/10.1021/cr9904009

41. Jensen F. Introduction to Computational Chemistry. (Odense: John Wiley & Sons, 2007).