Abstract
All kinds of different treatments for cancer have been proposed in the last years, being these mostly non-selective to neoplastic cells, but with the development of nanoscience, new approaches have developed, proposing nano-vectors as drug carriers and thus avoiding or diminishing the collateral and secondary effects of anticancer drugs. However, the structure, electronic properties, and protein interactions of these kinds of nanosystems have not been deeply studied. For this reason, we are proposing the design of three novel nano-devices against ovarian cancer, using a finite single-wall carbon nanotube functionalized with three commercial anticancer drugs (altretamine, melphalan, and cyclophosphamide) and glucosamine as solubilizing molecule, with a size range of 29.8 to 34.5 Å, which were characterized by a state-of-the-art methodology within density functional theory, obtaining their optimized structures, which were verified to be minima in the potential energy surfaces. We have calculated the changes in their electronic parameters, as compared with the respective free drugs; we also studied the interaction of these nano-vectors with KLK5, a protein overexpressed in ovarian cancer, which we suggest may contribute to the drug delivery process.
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Alexanian R et al (1969) Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens. J Am Med Assoc 208:1680–1685
Bhirde AA et al (2010) Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice. Nanomedicine 5:1535–1546
Bianco A, Kostarelos K, Partidos CD, Prato M (2005a) Biomedical applications of functionalised carbon nanotubes. Chem Commun (Camb) 7:571–577
Bianco A, Kostarelos K, Prato M (2005b) Applications of carbon nanotubes in drug delivery. Curr Opin Chem Biol 9:674–679
Díaz-Cervantes E, García-Revilla MA, Robles J, Aguilera-Granja F (2017) Solubility of functionalized single-wall carbon nanotubes in water: a theoretical study. Theor Chem Accounts 136:127
Dorn J et al (2011) Circulating biomarker tissue kallikrein-related peptidase KLK5 impacts ovarian cancer patients' survival. Ann Oncol 22:1783–1790
Fabbro C, Ali-Boucetta H, Ros TD, Kostarelos K, Bianco A, Prato M (2012) Targeting carbon nanotubes against cancer. Chem Commun 48:3911–3926
Fersht AR, Sperling J (1973) The charge relay system in chymotrypsin and chymotrypsinogen. J Mol Biol 74:137–149
Foster JP, Weinhold F (1980) Natural hybrid orbitals. J Am Chem Soc 102:7211–7218
Frisch MJ, Pople JA, Binkley JS (1984) Self-consistent molecular orbital methods 25. Supplementary functions for Gaussian basis sets. J Chem Phys 80:3265–3269
Hoppe-Tichy T (2010) Current challenges in European oncology pharmacy practice. J Oncol Pharm Pract 16:9–18
Humbel S, Sieber S, Morokuma K (1996) The IMOMO method: integration of different levels of molecular orbital approximations for geometry optimization of large systems: test for n-butane conformation and SN2 reaction: RCl+Cl−. J Chem Phys 105:1959–1967
Jmol: an open-source Java viewer for chemical structures in 3D
Klumpp C, Kostarelos K, Prato M, Bianco A (2006) Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim Biophys Acta 1758:404–412
Kostarelos K et al (2007) Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. Nat Nanotechnol 2:108–113
Kostarelos K et al (2009) Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat Nanotechnol 4:627–633
Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789
Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H (2008) Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res 68:6652–6660
Lu Y, Mahato RI (2009) Pharmaceutical perspectives of cancer therapeutics vol 1. 1 edn. doi:https://doi.org/10.1007/978-1-4419-0131-6_2
Markman M, Blessing JA, Moore D, Ball H, Lentz SS (1998) Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a gynecologic oncology group phase II. Tria Gynecol Oncol 69:226–229
Maseras F, Morokuma K (1995) IMOMM: a new integrated ab initio molecular mechanics geometry optimization scheme of equilibrium structures and transition states. J Comput Chem 16:1170–1179
McGuire WP et al (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334:1–6
Metzler DE (2003) Biochemistry: the chemical reactions of living vol 2, 2nd edn. Academic Press
Morokuma K (1977) Why do molecules interact? The origin of electron donor-acceptor complexes, hydrogen bonding and proton affinity. Acc Chem Res 10:294–300
Onsager L (1936) Electric moments of molecules in liquids. J Am Chem Soc 58:1486–1493
Parr RG, Yang W (1984) Density functional approach to the frontier-electron theory of chemical reactivity. J Am Chem Soc 106:4049–4050
Parr RG, Yang W (1989) Density functional theory of atoms and molecules, 1st edn. Oxford science publications, USA
Perdew JP, Burke K, Ernzerhof M (1996) Phys Rev Lett 77:3865–3868
Reed AE, Curtiss LA, Weinhold F (1988) Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem Rev 88:899–926
Robles J, López MJ, Alonso JA (2011) Modeling of the functionalization of single-wall carbon nanotubes towards its solubilization in an aqueous medium. Eur Phys J D 61:381–388
Sarin J, DeRossi SS, Akintoye SO (2008) Updates on bisphosphonates and potential pathobiology of bisphosphonate-induced jaw osteonecrosis. Oral Dis 14:277–285
Singh R et al (2005) Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors. J Am Chem Soc 127:4388–4396
Svensson M, Humbel S, Froese RDJ, Matsubara T, Sieber S, Morokuma K (1996) ONIOM: a multilayered integrated MO + MM method for geometry optimizations and single point energy predictions. A test for Diels−Alder reactions and Pt(P(t-Bu)3)2 + H2 oxidative addition. J Phys Chem 100:19357–19363
Tan DS-W, Gerlinger M, Teh B-T, Swanton C (2010) Anti-cancer drug resistance: understanding the mechanisms through the use of integrative genomics and functional RNA interference. Eur J Cancer 46:2166–2177
Thomsen R, Christensen MH (2006) MolDock: a new technique for high-accuracy molecular docking. J Med Chem 49:3315–3321
Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093
Vardharajula S, Ali SZ, Tiwari PM, Eroğlu E, Vig K, Dennis VA, Singh SR (2012) Functionalized carbon nanotubes: biomedical applications. Int J Nanomedicine 7:5361–5374
Warshel A (1978) Energetics of enzyme catalysis. Proc Natl Acad Sci 75:5250–5254
Yang J, Chen C (2004) GEMDOCK: a generic evolutionary method for molecular docking. Proteins 55:288–304
Yousef GM, Obiezu CV, Jung K, Stephan C, Scorilas A, Diamandis EP (2002) Differential expression of Kallikrein gene 5 in cancerous and normal testicular tissues. Urology 60:714–718
Acknowledgements
We are grateful to the Laboratorio Nacional de Caracterización de Propiedades Fisicoquímicas y Estructura Molecular (UG-UAA-CONACYT, Project: 123732) for the computing time provided at the PIPILA cluster.
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E. Díaz-Cervantes acknowledge the received support from a postdoctoral scholarship from PRODEP at UASLP
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Díaz-Cervantes, E., Robles, J. & Aguilera-Granja, F. Understanding the structure, electronic properties, solubility in water, and protein interactions of three novel nano-devices against ovarian cancer: a computational study. J Nanopart Res 20, 266 (2018). https://doi.org/10.1007/s11051-018-4362-8
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DOI: https://doi.org/10.1007/s11051-018-4362-8