Nanotransporters for anticancer drugs, modifications, target molecules

The concept of using a particle measured in the nanoscale as carriers of drugs and vaccines appeared over three decades ago. Advances in nano medicine has evolved and has raised hopes for the implementation methods of striking antitumor therapy selectively in tumor mass, while reducing the risk of a wide range of side effects, which are encumbering modern pharmacology. Nanoparticles are attractive as drug delivery platforms because it is relatively easy to influence their properties and modify their features, so that they can be useful in creation of effective and precise medicine carriers. Meaningful are not only dimensions of the carrier enabling tissue penetration, but also their shape, and developed different functionalities of surface. Current progress in the field of nanobiotechnology has led to the development of a new area of nanomedicine, associated with the application of nano biomaterials, both for diagnostic and therapeutic aims creating a new category of nano particles called theranostics. The main expectations and challenges in this regard relate to nano-magnetic properties, received bioengineering methods, with potential used in the transport of drugs, particularly anticancer drugs used in therapy determined using molecular targets. Unique physicochemical properties of magnetic nanoparticles promise hope for the development of modern cancer nanomedicine, acting, inter alia, technological breakthrough in the area of targeted drug delivery and gene therapy of cancer using magnetic hyperthermia, tissue engineering, marking the tumor cells and the molecular magnetic resonance imaging. Nanotechnology in medicine and health care was initiated over forty years ago with deliverance of the first therapeutic and diagnostic agents in a safer and more efficient manner [1]. Convergention of diagnosis and therapy carried out through exploitation of nanoparticles resulted with increasing number of theradiagnostics went out from research stage and being commercialized or having reached clinical stage.

1. Strebhardt, K.; Ullrich, A. Paul ehrlich‘s magic bullet concept: 100 years of progress. Nat. Rev. Cancer 2008, 8, 473-480.
2. Geim, A.K.; Novoselov, K.S. The rise of graphene. Nat. Mater. 2007, 6, 183-191.
3. Terranova, M.L.; Sessa, V.; Rossi, M. The world of carbon nanotubes: An overview of cvd growth methodologies. Chem. Vapor Depos. 2006, 12, 315-325.
4. Tripisciano, C.; Kraemer, K.; Taylor, A.; Borowiak-Palen, E. Single-wall carbon nanotubes based anticancer drug delivery system. Chem. Phys. Lett. 2009, 478, 200-205.
5. Ali-Boucetta, H.; Al-Jamal, K.T.; Kostarelos, K. Multi-walled carbon nanotube-doxorubicin supramolecular complexes for cancer therapeutics. Crc Press-Taylor & Francis Group: Boca Raton, 2008; p 16-18.
6. Hampel, S.; Kunze, D.; Haase, D.; Kramer, K.; Rauschenbach, M.; Ritscbel, M.; Leonbardt, A.; Thomas, J.; Oswald, S.; Hoffmann, V., et al. Carbon nanotubes filled with a chemotherapeutic agent: A nanocarrier mediates inhibition of tumor cell growth. Nanomedicine 2008, 3, 175-182.
7. Bianco, A.; Kostarelos, K.; Prato, M. Applications of carbon nanotubes in drug delivery. Curr. Opin. Chem. Biol. 2005, 9, 674-679.
8. Prato, M.; Kostarelos, K.; Bianco, A. Functionalized carbon nanotubes in drug design and discovery. Accounts Chem. Res. 2008, 41, 60-68.
9. Cui, D.X.; Tian, F.R.; Ozkan, C.S.; Wang, M.; Gao, H.J. Effect of single wall carbon nanotubes on human hek293 cells. Toxicol. Lett. 2005, 155, 73-85.
10. Pastorin, G.; Wu, W.; Wieckowski, S.; Briand, J.P.; Kostarelos, K.; Prato, M.; Bianco, A. Double functionalisation of carbon nanotubes for multimodal drug delivery. Chem. Commun. 2006, 1182-1184.
11. Pantarotto, D.; Singh, R.; McCarthy, D.; Erhardt, M.; Briand, J.P.; Prato, M.; Kostarelos, K.; Bianco, A. Functionalized carbon nanotubes for plasmid DNA gene delivery. Angew. Chem.-Int. Edit. 2004, 43, 5242-5246.
12. Singh, R.; Pantarotto, D.; McCarthy, D.; Chaloin, O.; Hoebeke, J.; Partidos, C.D.; Briand, J.P.; Prato, M.; Bianco, A.; Kostarelos, K. Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: Toward the construction of nanotube-based gene delivery vectors. J. Am. Chem. Soc. 2005, 127, 4388-4396.
13. Ito, A.; Shinkai, M.; Honda, H.; Kobayashi, T. Medical application of functionalized magnetic nanoparticles. J. Biosci. Bioeng. 2005, 100, 1-11.
14. Mnneil, S.E. Nanotechnology for the biologist. J. Leukoc. Biol. 2005, 78, 585-594.
15. Jain, T.K.; Richey, J.; Strand, M.; Leslie-Pelecky, D.L.; Flask, C.A.; Labhasetwar, V. Magnetic nanoparticles with dual functional properties: Drug delivery and magnetic resonance imaging. Biomaterials 2008, 29, 4012-4021.
16. Sun, C.; Lee, J.S.H.; Zhang, M.Q. Magnetic nanoparticles in mr imaging and drug delivery. Adv. Drug Deliv. Rev. 2008, 60, 1252-1265.
17. Harisinghani, M.G.; Barentsz, J.; Hahn, P.F.; Deserno, W.M.; Tabatabaei, S.; van de Kaa, C.H.; de la Rosette, J.; Weissleder, R. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N. Engl. J. Med. 2003, 348, 2491-U2495.
18. Maier-Hauff, K.; Rothe, R.; Scholz, R.; Gneveckow, U.; Wust, P.; Thiesen, B.; Feussner, A.; von Deimling, A.; Waldoefner, N.; Felix, R., et al. Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: Results of a feasibility study on patients with glioblastoma multiforme. J. Neuro-Oncol. 2007, 81, 53-60.
19. Hofheinz, R.D.; Gnad-Vogt, S.U.; Beyer, U.; Hochhaus, A. Liposomal encapsulated anti-cancer drugs. Anti-Cancer Drugs 2005, 16, 691-707.
20. Allen, T.M.; Cullis, P.R. Liposomal drug delivery systems: From concept to clinical applications. Adv. Drug Deliv. Rev. 2013, 65, 36-48.
21. Huynh, N.T.; Passirani, C.; Saulnier, P.; Benoit, J.P. Lipid nanocapsules: A new platform for nanomedicine. Int. J. Pharm. 2009, 379, 201-209.
22. Sharma, A.; Sharma, U.S. Liposomes in drug delivery: Progress and limitations. Int. J. Pharm. 1997, 154, 123-140.
23. Gabizon, A.A. Stealth liposomes and tumor targeting: One step further in the quest for the magic bullet. Clin. Cancer Res. 2001, 7, 223-225.
24. Romberg, B.; Hennink, W.E.; Storm, G. Sheddable coatings for long-circulating nanoparticles. Pharm. Res. 2008, 25, 55-71.
25. Zamboni, W.C.; Ramalingam, S.; Friedland, D.M.; Edwards, R.P.; Stoller, R.G.; Strychor, S.; Maruca, L.; Zamboni, B.A.; Belani, C.P.; Ramanathan, R.K. Phase i and pharmacokinetic study of pegylated liposomal ckd-602 in patients with advanced malignancies. Clin. Cancer Res. 2009, 15, 1466-1472.
26. Boulikas, T. Clinical overview on lipoplatin (tm): A successful liposomal formulation of cisplatin. Expert Opin. Investig. Drugs 2009, 18, 1197-1218.
27. Canta, A.; Chiorazzi, A.; Carozzi, V.; Meregalli, C.; Oggioni, N.; Sala, B.; Crippa, L.; Avezza, F.; Forestieri, D.; Rotella, G., et al. In vivo comparative study of the cytotoxicity of a liposomal formulation of cisplatin (lipoplatin (tm)). Cancer Chemother. Pharmacol. 2011, 68, 1001-1008.
28. Casagrande, N.; De Paoli, M.; Celegato, M.; Borghese, C.; Mongiat, M.; Colombatti, A.; Aldinucci, D. Preclinical evaluation of a new liposomal formulation of cisplatin, lipoplatin, to treat cisplatin-resistant cervical cancer. Gynecol. Oncol. 2013, 131, 744-752.
29. Wang, R.H.; Cao, H.M.; Tian, Z.J.; Jin, B.; Wang, Q.; Ma, H.; Wu, J. Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer. Oncol. Rep. 2015, 33, 783-791.
30. Mei, L.; Fu, L.; Shi, K.R.; Zhang, Q.Y.; Liu, Y.Y.; Tang, J.; Gao, H.L.; Zhang, Z.R.; He, Q. Increased tumor targeted delivery using a multistage liposome system functionalized with rgd, tat and cleavable peg. Int. J. Pharm. 2014, 468, 26-38.
31. Wang, F.F.; Chen, L.; Zhang, R.; Chen, Z.P.; Zhu, L. Rgd peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer. J. Control. Release 2014, 196, 222-233.
32. Theil, E.C.; Liu, X.F.S.; Tosha, T. Gated pores in the ferritin protein nanocage. Inorg. Chim. Acta 2008, 361, 868-874.
33. Yang, Z.; Wang, X.Y.; Diao, H.J.; Zhang, J.F.; Li, H.Y.; Sun, H.Z.; Guo, Z.J. Encapsulation of platinum anticancer drugs by apoferritin. Chem. Commun. 2007, 3453-3455.
34. Xing, R.M.; Wang, X.Y.; Zhang, C.L.; Zhang, Y.M.; Wang, Q.; Yang, Z.; Guo, Z.J. Characterization and cellular uptake of platinum anticancer drugs encapsulated in apoferritin. J. Inorg. Biochem. 2009, 103, 1039-1044.
35. Falvo, E.; Tremante, E.; Fraioli, R.; Leonetti, C.; Zamparelli, C.; Boffi, A.; Morea, V.; Ceci, P.; Giacomini, P. Antibody-drug conjugates: Targeting melanoma with cisplatin encapsulated in protein-cage nanoparticles based on human ferritin. Nanoscale 2013, 5, 12278-12285.
36. Yan, F.; Zhang, Y.; Yuan, H.K.; Gregas, M.K.; Vo-Dinh, T. Apoferritin protein cages: A novel drug nanocarrier for photodynamic therapy. Chem. Commun. 2008, 4579-4581.
37. Zhen, Z.P.; Tang, W.; Chen, H.M.; Lin, X.; Todd, T.; Wang, G.; Cowger, T.; Chen, X.Y.; Xie, J. Rgd-modified apoferritin nanoparticles for efficient drug delivery to tumors. ACS Nano 2013, 7, 4830-4837.
38. Ma-Ham, A.H.; Wu, H.; Wang, J.; Kang, X.H.; Zhang, Y.Y.; Lin, Y.H. Apoferritin-based nanomedicine platform for drug delivery: Equilibrium binding study of daunomycin with DNA. J. Mater. Chem. 2011, 21, 8700-8708.
39. Kilic, M.A.; Ozlu, E.; Calis, S. A novel protein-based anticancer drug encapsulating nanosphere: Apoferritin-doxorubicin complex. J. Biomed. Nanotechnol. 2012, 8, 508-514.
40. Blazkova, I.; Nguyen, H.V.; Dostalova, S.; Kopel, P.; Stanisavljevic, M.; Vaculovicova, M.; Stiborova, M.; Eckschlager, T.; Kizek, R.; Adam, V. Apoferritin modified magnetic particles as doxorubicin carriers for anticancer drug delivery. Int. J. Mol. Sci. 2013, 14, 13391-13402.
41. Gumulec, J.; Fojtu, M.; Raudenska, M.; Sztalmachova, M.; Skotakova, A.; Vlachova, J.; Skalickova, S.; Nejdl, L.; Kopel, P.; Knopfova, L., et al. Modulation of induced cytotoxicity of doxorubicin by using apoferritin and liposomal cages. Int. J. Mol. Sci. 2014, 15, 22960-22977.

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