Ultrasound transducer element arrays using acoustic ensonification drive patterns via a patient interface for sonosensitizer activation in sonodynamic therapy. Incoherent acoustic field generation varying phase, frequencies, and/or amplitude via controlled delivery of low intensity planar acoustic waves. Method includes generating a first and a second signal to generate respective acoustic ensonification drive patterns with phase, frequency, and amplitude and generating at least one relative phase, frequency or amplitude difference to generate a third incoherent acoustic ensonification pattern to activate a sonosensitizer. Calibration and complementary therapy procedures to improve cell susceptibility of cells to sonodynamic therapy are disclosed.

Described in several embodiments herein are injectable hydrogels that are capable of attracting one or more cells, in situ. In some embodiments, the cells are cancer cells, such as cancer stem cells. Also described herein are methods of using the injectable hydrogels to fill a cavity in a subject. Also described herein are methods of treating a cancer by injecting an injectable hydrogel in a cavity in a subject formed from resecting a tumor and applying an external stimulus to the injected injectable hydrogel or area proximate to the injected injectable hydrogel.

Methods of treating tumors by administering compounds to a patient are provided. Compounds such as drugs, may be administered to the patient orally, by injection, intravenously, or topically, which then accumulate preferentially as compounds such as protoporphyrin IX (PpIX) in tumor cells. After such accumulation, compounds such as PpIX are then activated in various aspects to treat tumors cells, thereby treating cancer. Cancers such as glioblastoma may be treated.

The present invention relates to: a toll-like receptor 7 or 8 agonist-drug complex material in which a functional drug and a toll-like receptor 7 or 8 agonist are bonded by a chemical bond containing a cleavable site; and using the properties of the temporarily inactivated state, the side effects of the toll-like receptor 7 or 8 agonist can be reduced. In particular, the complex material is designed such that the immunostimulatory function of the toll-like receptor 7 or 8 agonist is inhibited due to the chemical bond, while the immunostimulatory function is recovered at an injection site or in a tumor microenvironment or target immune cells, thus exhibiting kinetic properties in which immunostimulatory efficacy can be controlled over time, and minimizing the induction of nonspecific immune responses. In addition, since various functions can be combined with a drug, the inactivated toll-like receptor 7 or 8 agonist-functional drug complex can be widely used in pharmaceutical compositions for various applications, which are capable of controlling cancer cell death, the activation of therapeutic immune cells, and immunosuppressive cells and environments, at an injection site or in a tumor microenvironment.

Disclosed are methods of using planar acoustic waves for providing non-invasive sonodynamic therapy. The method includes acoustically coupling an array of flat piezoelectric transducers to a patient. A controller is configured to generate an electrical drive signal at a frequency selected from a range of frequencies, modulate the drive signal, and drive the transducer with the modulated drive signal at the frequency to produce a modulated planar acoustic wave to produce an average acoustic intensity sufficient to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.

Disclosed are nanoparticle-based ultrasound contrast agents that comprise a sub-100 nanometer nanoparticle core, a hydrophobic layer, and a stabilization layer, and methods of producing such ultrasound contrast agents. The stabilization layer comprises molecules that are spaced apart on the stabilization layer to provide bubble nucleation sites that initiate cavitation of the bubbles in response to acoustic intensity delivered by ultrasound equipment.

A method for destroying cells and/or microorganisms in an organism includes the following steps: (a) administering to the organism a composition including a sonosensitizing compound containing at least one transition metal with three bidentate ligands; and (b) exposing the sonosensitizing compound in the organism to ultrasound, wherein the ultrasound is effective to activate the sonosensitizing compound to destroy at least one of the cells and the microorganisms in the organism. The ultrasound is preferably used in conjunction with electromagnetic therapies comprising photodynamic therapy, low-level laser therapy, and radiation therapy. The ultrasound is preferably administered at a duty cycle in the range from 5% to 95% at a power density of 10 W/cm.sup.2 and a frequency in the range from 10 Hz to 10 MHz.

Disclosed are methods of using focused acoustic waves for providing non-invasive sonodynamic therapy. The method includes acoustically coupling an array of piezoelectric transducers to a patient. A controller is configured to generate an electrical drive signal at a frequency selected from a range of frequencies, modulate the drive signal, and drive the transducer with the modulated drive signal at the frequency to produce modulated acoustic waves to produce an average acoustic intensity sufficient to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.

Disclosed are methods of using planar or defocused acoustic waves for providing non-invasive sonodynamic therapy. The method includes acoustically coupling an array of piezoelectric transducers to a patient. A controller is configured to generate an electrical drive signal at a frequency selected from a range of frequencies, modulate the drive signal, and drive the transducer with the modulated drive signal at the frequency to produce modulated acoustic waves to produce an average acoustic intensity sufficient to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.

Disclosed are methods of producing ultrasound waves for providing sonodynamic therapy. The method includes coupling a sonodynamic therapy device with an array of piezoelectric transducer elements to a skin surface. A controller is configured to generate an electrical drive signal to produce ultrasound waves to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.