of work:Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effects of cell killing by a combination of sonosensitzer and ultrasound. Ultrasound can penetrate deeply into tissue and can be focused in a small region of tumor to activate non-toxic molecules (e.g. porphyrins ) thus minimizing undesirable side effects. The experimental evidence suggests that sonosensitization is due to the chemical activation of sonosensitizers inside or in close vicinity of hot collapsing cavitation bubbles to form sensitizer-derived radicals either by direct pyrolysis of the sensitizer at the water-gas interface or due to the reactions of hydrogen atoms and hydroxyl radicals formed by the pyrolysis of water. The free radicals derived from the sonosensitizer (mostly carbon-centered) react with oxygen to form peroxyl and alkoxyl radicals. Unlike OH radicals and H atoms which are formed by pyrolysis inside cavitation bubbles, the reactivity of alkoxyl and peroxyl radicals with organic compounds in biological media is much lower and hence they have a higher probability of reaching critical cellular sites.The mechanism(s) responsible for sudden cytolysis observed when cells are exposed to ultrasound could be mechanical and/or free radical in nature. Free radical reactions are initiated in the core and in the interfacial regions of collapsing acoustic cavitation bubbles. Since cyclic sugars are known to inhibit free radical chain reactions, we investigated the effect of n-alkyl a-D glucopyranosides of varying hydrophobicity on ultrasound (1.057 MHz) induced cytolysis of HL-60 cells in vitro. n-alkyl glucopyranosides with hexyl- (HGP, 5 mM), heptyl- (3 mM) or octyl- (2 mM) n-alkyl chains protected 100% of the cell population from ultrasound induced cytolysis under conditions where 35% to 100% cytolysis occurred in the absence of glucopyranosides. The protected cell populations also possessed long-term reproductive viability. However, the hydrophilic methyl-a-D glucopyranoside could not protect cells, even up to a concentration of 30 mM. Furthermore, none of the glucopyranosides could prevent cytolysis of cells from a mechanically induced shear stress. Spin trapping and electron spin resonance experiments confirmed the presence of inertial cavitation in cell suspensions both in the presence and absence of the surfactants. It is concluded that surface active glucopyranosides efficiently quench cytotoxic radicals at the gas/solution interface of collapsing cavitation bubbles.1. Feril, L.B., Tsuda, Y., Kondo, T., Zhao, Q.L., Ogawa, R., Cui, Z.G., Tsukada, K. & Riesz P., Ultrasound-induced killing of monocytic U937 cells enhanced by 2,2'-azobis(2-amidinopropane) dihydrochloride. Cancer Science 95, 181-185 (2004).2. Feril, L., Kondo, T., Takaya, K. & Riesz, P., Enhanced ultrasound-induced apoptosis and cell lysis by a hypotonic medium. International Journal Of Radiation Biology 80, 165-175 (2004).3. Rosenthal, I., Sostaric, J. & Riesz, P., Sonodynamic therapy - a review of the synergistic effects of drugs and ultrasound. Ultrasonics Sonochemistry 11, 349-363 (2004).4. Rosenthal, I., Sostaric, J. & Riesz, P., Enlightened sonochemistry. Research On Chemical Intermediates 30, 685-701 (2004).5. Sostaric, J., Miyoshi, N., Riesz, P., De Graff, W.G., Mitchell, J.B., n-Alkyl glucopyranosides completely inhibit ultrasound induced cytolysis. (Free Radicals Biology and Medicine, In Press, 2005)

Agency
National Institute of Health (NIH)
Institute
Division of Clinical Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC006358-23
Application #
7331386
Study Section
(RBB)
Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Buldakov, Mikhail A; Hassan, Mariame A; Zhao, Qing-Li et al. (2009) Influence of changing pulse repetition frequency on chemical and biological effects induced by low-intensity ultrasound in vitro. Ultrason Sonochem 16:392-7
Sostaric, Joe Z (2008) A comparative sonochemical reaction that is independent of the intensity of ultrasound and the geometry of the exposure apparatus. Ultrason Sonochem 15:1043-8
Sostaric, Joe Z (2008) A chemical sensor that can detect the frequency of ultrasound. J Am Chem Soc 130:3248-9
Cheng, Jason Y; Riesz, Peter (2007) Mechanism of the protective effects of long chain n-alkyl glucopyranosides against ultrasound-induced cytolysis of HL-60 cells. Ultrason Sonochem 14:667-71
Sostaric, Joe Z; Miyoshi, Norio; Riesz, Peter et al. (2005) n-Alkyl glucopyranosides completely inhibit ultrasound-induced cytolysis. Free Radic Biol Med 39:1539-48
Feril Jr, Loreto B; Tsuda, Yuko; Kondo, Takashi et al. (2004) Ultrasound-induced killing of monocytic U937 cells enhanced by 2,2'-azobis(2-amidinopropane) dihydrochloride. Cancer Sci 95:181-5
Feril Jr, L B; Kondo, T; Takaya, K et al. (2004) Enhanced ultrasound-induced apoptosis and cell lysis by a hypotonic medium. Int J Radiat Biol 80:165-75
Rosenthal, Ionel; Sostaric, Joe Z; Riesz, Peter (2004) Sonodynamic therapy--a review of the synergistic effects of drugs and ultrasound. Ultrason Sonochem 11:349-63