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202    CHAPTER 8  Ultrasound applications in cancer therapy




                         area. Microspheres have four different types: Bioadhesive microspheres that exhibit
                         mucoadhesive property and permits the drug-coated on the surface of the polymer to
                         stick to the targeted organ, resulting in prolonged delivery of the therapeutic agents
                         to the diseased site. Magnetic microspheres which can be used for both diagnos-
                         tic purposes and drug delivery. The drugs within these particles can be targeted to
                         the diseased area using an external magnetic source [68]. Also, they are commonly
                         utilized for magnetic hyperthermia in tumor tissues. Floating microspheres that are
                         meant to release the drugs loaded in them in gastric content. Radioactive particles
                         which are used for the therapeutic purpose. They directly inject in the veins and link
                         to the targeted organ or tissue.


                         8.4.2  Sonodynamic therapy (SDT)
                         Sonodynamic therapy (SDT) is an emerging approach that involves a combination
                         of low-intensity ultrasound and specialized chemical agents known as sonosensitiz-
                         ers. This method has been developed as a novel promising noninvasive approach
                         derived from photodynamic therapy (PDT), that is mediated via ultrasound-induced
                         cavitation and sonosensitizers to produce free radicals to kill dividing cancer cells.
                         The SDT method is used to treat deeply located tumors, however, PDT utilizes vis-
                         ible light, which has limited penetration, and can only be employed superficially
                         or intraoperatively. Jin et al. found that SDT inhibited tumor growth by 77%, com-
                         pared with 27% for PDT in a subcutaneously located murine squamous cell carci-
                         noma [69]. To improve the efficacy of treating solid tumors, it is important that the
                         sonosensitizer is injected intravenously prior to insonation, rather than directly into
                         the tumor, so that it is more fully and evenly distributed throughout the neoplasm
                         [70].In  SDT,  the  sonication  parameters  (usually  1.0–2.0  MHz  at  an  intensity  of
                         0.5–3.0 W cm) have been selected to produce inertial cavitation in a cell culture or
                         tumor, where a bubble in a liquid rapidly collapses, producing a shock wave which
                         produces free radicals and a cascade of molecular events that activate the sonosen-
                         sitizer and in turn damage the cancer cells [71]. Gao et al. reported that SDT also
                         had an antivascular effect and inhibited tumor neovascularization [72]. Combining
                         PDT with SDT had a synergistic effect in solid tumors with additional posttherapy
                         tumor necrosis, inhibition of tumor growth and increased survival times [71]. The
                         combining of the sonosensitizer with a microbubble contrast agent provides new
                         developments in SDT [73].
                            The sonication parameters in SDT (usually 1.0–2.0  MHz at an intensity of
                                    2
                         0.5–3.0 W/cm ) have been selected to produce cavitation in a cell culture or tumor.
                         Cavitation process involves the nucleation, growth, and implosive collapse of gas-
                         filled bubbles under the appropriate ultrasound conditions. It may be essentially
                         classified into stable and inertial cavitation 14. Bubbles of stable cavitation oscil-
                         late, creating a streaming of the surrounding liquid which results in a mixture of
                         the surrounding media while the gas bubbles in inertial cavitation process grow to a
                         near resonance size and expand to a maximum before collapse violently 18. Further,
                         insonation of the microbubble may lead to an additional significant local thermal
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