Using the Promise of Sonodynamic Therapy in the Clinical Setting against Disseminated Cancers

Table 2

Sonosensitizers tested in sonodynamic therapy.

Sonosensitizer	Class	Primary mechanism	Synergistic effect with ultrasound
Doxorubicin (Adriamycin)	Anthracycline	It intercalates DNA, preventing DNA replication and protein synthesis	Increased efficacy with multidrug resistant K562/A02 cells at 20 kHz, 0.25 W/cm^2, 60 s intervals [85]; similar effects observed with U937 cells [62]; the agent can be used in tandem with HMME on U937 cells for a greater effect [88]
Cytochalasin B	Cytoskeleton agent	It disrupts actin cytoskeleton and prevents cytokinesis by interfering with formation of the contractile ring as well as the cleavage furrow; cells do not divide and become grossly enlarged and multinucleated	Sonic sensitivity was increased in U937 cells when cytochalasin B was administered at 1.5 μM; cells often grew to 20 μm or greater and were unable to tolerate ultrasound treatments in which normal blood remained stable; increased mitochondrial activity and reduced clonogenicity were also observed [89]; cytochalasin B sensitized multiple leukemia cell lines (U937, THP1, K562, Molt-4, and L1210) to 20 kHz and 23.5 kHz ultrasound [90]
Methotrexate	Cytoskeleton agent, antimetabolite agent	It causes competitive inhibition of dihydrofolate reductase, an enzyme that participates in tetrahydrofolate synthesis, prevents production of thymidine as well as all purine bases, and causes the same effects on the cytoskeleton as cycloplatin	Aberrant features with the cytoskeleton of HeLa cells were observed using 1.8 MHz, 0.22 W/cm^2 [110]
Cisplatin	DNA alkylating agent	It alkylates guanine nucleotides, preventing DNA synthesis	Increased cytotoxicity to multiple cancer types; ultrasound replenishes labile cells lost due to treatments [6]
Diaziquone	DNA alkylating agent	It alkylates guanine nucleotides, preventing DNA synthesis	Increased cytotoxicity to multiple cancer types; ultrasound has the same effects on depleted labile cells [6]
Albunex	Echo contrast agent	It increases microbubbles in systemic circulation to enhance effects of inertial cavitation	Macrocytic (grossly enlarged) erythrocytes were damaged by the increased proportion of microbubbles at intensities that left normal erythrocytes intact using 1.15 MHz, 3 MPa, indicating SDT preferentially damages based on size [15, 111]
Levovist	Echo contrast agent	It increases microbubbles in systemic circulation to enhance effects of inertial cavitation; cells exposed to drug treatment have low mitochondrial membrane potential, high superoxide production, increased intracellular calcium concentration, and phosphorylation of histone H2AX after sonication	Multiple leukaemia cell lines (Jurkat, Molt-4, U937) were significantly damaged Using 1 MHz, 0.3 W/cm^2, 10% duty factor pulsed at 100 Hz [112]
ATX-S10	ROS agent, porphyrin	It has a substantially longer sonoluminescent lifetime than other porphyrin agents, providing more opportunity to generate singlet oxygen; it follows the same mechanism as other porphyrins	Inhibited growth of colon-26 cells injected into athymic mice [6]
Hematoporphyrin monomethyl ether (HMME)	ROS agent, porphyrin	It generates singlet oxygen that disrupts mitochondrial membrane potential, loss of electrochemical gradient, causes cristae to fragment, and induces apoptotic cascade to trigger caspase proteases	Significant destruction of U937 cells with 1 MHz, 1 W/cm^2, 60 s intervals, increases intracellular singlet oxygen content [113], showing synergistic effect with DOX as both produce ROS [88]

All agents were shown to have increased efficacy due to ultrasound-activating mechanisms.