Abstract
Introduction: Recently, ultrasonic drug release has been a focus of many research groups for stimuli responsive drug release. It has been demonstrated that a focused ultrasound (FUS) beam rapidly increases the temperature at the focused tissue area. One potential mechanism of drug targeting is to utilize the induced heat to release or increase penetration of chemotherapy to cancer cells. The efficiency of targeted drug delivery may increase by using FUS beam in conjugation with nano-encapsulated drug carriers.
The aim of this study is to investigate the effect of heat and ultrasound on the cellular uptake and therapeutic efficacy of an anticancer drug using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS).
Materials and Methods: Human KB cells (CCL-17 cells) were seeded into 96-well plates and heat treated at 37–55°C for 2–10 min. Cell viability was determined using the colorimetric MTT assay. The cells were also subjected to MRgFUS and the degree of cell viability was determined. These experiments were conducted using an ExAblate 2000 system (InSightec, Haifa, Israel) and a GE 1.5 T MRI system, software release 15.
Results: We have observed a significant decrease in human KB cell viability due to heat (>41°C) in the presence of Doxorubicin (DOX), in comparison with DOX at normal culture temperature (37°C). The synergistic effect of heat with DOX may be explained by several mechanisms. One potential mechanism may be increased penetration of DOX to the cells during heating. In addition, we have shown that ultrasound induced cavitation causes cell necrosis.
Discussion and Future work: Further investigation is required to optimize the potential of MRgFUS to enhance cellular uptake of therapeutic agents. A novel delivery nano-vehicle developed by CapsuTech will be investigated with MRgFUS for its potential as a stimuli responsive delivery system.
Acknowledgments: This work is supported by an EU FP7 Industrial Academia Partnership Pathway IAPP.
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References
Akiyama, S., et al. (1985). Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somatic Cell and Molecular Genetics, 11(2), 117–126.
Aschkenasy, C., & Kost, J. (2005). On-demand release by ultrasound from osmotically swollen hydrophobic matrices. Journal of Controlled Release, 110, 58–66.
Banerjee Shashwat S., & Dong-Hwang Chen (2009). Cyclodextrin-conjugated nanocarrier for magnetically guided delivery of hydrophobic drugs. J Nanopart Res, 11, 2071–2078.
Battistini, E., et al. (2008). High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-β-cyclodextrin. Chemistry – A European Journal, 14, 4551–4561.
Brennen, C. E. (1995). Cavitation and bubble dynamics. New York: Oxford University Press.
Brewster, M. E., & Loftsson, T. (2007). Cyclodextrins as pharmaceutical solubilizers. Advanced Drug Delivery Reviews, 59, 645–666.
Brouwers, J., et al. (2009). Supersaturating drug delivery systems: The answer to solubility- limited oral bioavailability? Journal of Pharmaceutical Sciences, 98, 2549–2572.
Cabral Marques, H. M. (2010). A review on cyclodextrin encapsulation of essential oils and volatiles. Flavour and Fragrance Journal, 25, 313–326.
Challa, R., et al. (2005). Cyclodextrins in drug delivery: An updated review. AAPS PharmSciTech, 6(2) Article 43, p. E329–E357.
Dromi, S., et al. (2007). Pulsed-high intensity focused ultrasound and low temperature sensitive liposomes for enhanced targeted drug delivery and antitumor effect. Clinical Cancer Research, 13(9), 2722–2727.
Duchene, D., et al. (1999). Cyclodextrins in targeting application to nanoparticles. Advanced Drug Delivery Reviews, 36, 29–40.
Figuerola, A., et al. (2010). From iron oxide nanoparticles towards advanced iron-based inorganic materials designed for biomedical applications. Pharmacological Research. doi:10.1016/j.phrs.2009.12.012.
Freeman, A. I., & Mayhew, E. (1986). Targeted drug delivery. Cancer, 58, 573–583.
Gerold, B., et al. (2011). Laser-nucleated acoustic cavitation in focused ultrasound. Review of Scientific Instruments, 82(4), 044902.
Glaser, V. (2001). Current trends and innovations in cell culture. Genetic Engineering, 21(11).
Hallow, D. M., et al. (2006). Measurement and correlation of acoustic cavitation with cellular bioeffects. Ultrasound in Medicine & Biology, 32, 1111–1122.
Hennache, B., & Boulanger, P. (1977). Biochemical study of KB-cell receptor to adenovirus. Biochemical Journal, 166, 237–247.
Jolesz, F. A., & McDannold, N. (2008). Current status and future potential of MRI-guided focused ultrasound surgery. Journal of Magnetic Resonance Imaging, 27, 391–399.
Leighton, T.G. (1994). The acoustic bubble. Academic Press.
Loftsson, T., et al. (2007). Effects of cyclodextrins on drug delivery through biological membranes. Journal of Pharmaceutical Sciences, 96(10), 2532–2546.
Maestrelli, F., et al. (2005). Preparation and characterisation of liposomes encapsulating ketoprofen–cyclodextrin complexes for transdermal drug delivery. International Journal of Pharmaceutics, 298, 55–67.
Marmottant, P., & Hilgenfeldt, S. (2003). Controlled vesicle deformation and lysis by single oscillating bubbles. Nature, 423, 153.
Middleton, M. A., et al. (2000). Four-hourly scheduling of temozolomide improves tumour growth delay but not therapeutic index in A375M melanoma xenografts. Cancer Chemotherapy and Pharmacology, 45, 15–20.
Ohl, C. D., et al. (2006). Sonoporation from jetting cavitation bubbles. Biophysical Journal, 91(11), 4285–4295.
Patri, A. K., et al. (2005). Targeted drug delivery with dendrimers: Comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Advanced Drug Delivery Reviews, 57, 2203–2214.
Pitt, W.G., et al. (2006). Ultrasonic drug delivery – A general review. Expert Opinion on Drug Delivery. Author manuscript; available in PMC 2006 February 6.
Prentice, P. (2006). Membrane disruption by optically controlled cavitation. PhD Thesis, University of Dundee.
Pua, E.C., & Zhong, P. (2009 Jan–Feb). Ultrasound-mediated drug delivery. IEEE Engineering in Medicine Biology Magazine, 64–75.
Schroeder, A., et al. (2009). Ultrasound, liposomes, and drug delivery: Principles for using ultrasound to control release of drugs from liposomes. Chemistry and Physics of Lipids, 162, 1–16.
Seftor, R.E.B., et al. (1992). Role of the alphaVbeta integrin in human melanoma cell invasion. Proc. Natl. Acad. Sci. USA. Vol. 89, 1557–1561.
Staruch, R., et al. (2011). Localised drug release using MRI-controlled focused ultrasound hyperthermia. Int J Hyperthermia, 27(2), 156–171.
Stella, Valentino J., & Quanren, He. (2008). Cyclodextrins. Toxicologic Pathology, 36, 30–42.
Tachibana, K., & Tachibana, S. (2001). The use of ultrasound for drug delivery. Echocardiography, 18, 323–328.
Uekama, K., et al. (1997). 6-O-[(4-Biphenylyl)acetyl]-α-,-β- and -γ-cyclodextrins and 6-Deoxy- 6-[[(4-biphenylyl)acetyl]amino]-α-,-β, and -γ-cyclodextrins: Potential prodrugs for colon- specific delivery. Journal of Medical Chemistry, 40, 2755–2761.
van de Manakker, F., et al. (2009). Cyclodextrin-based polymeric materials: Synthesis, properties, and pharmaceutical/biomedical applications. Biomacromolecules, 10, 3157–3175.
Wang, J., & Jiang, M. (2006). Polymeric self-assembly into micelles and hollow spheres with multiscale cavities driven by inclusion complexation. Journal of the American Chemical Society, 128, 3703–3708.
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This work is supported by an EU FP7 Industrial Academia Partnership Pathway IAPP.
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Gourevich, D. et al. (2012). Ultrasound Activated Nano-Encapsulated Targeted Drug Delivery and Tumour Cell Poration. In: Zahavy, E., Ordentlich, A., Yitzhaki, S., Shafferman, A. (eds) Nano-Biotechnology for Biomedical and Diagnostic Research. Advances in Experimental Medicine and Biology, vol 733. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2555-3_13
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