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.

The present inventions provides drug-drug conjugates, drug-porphyrin conjugates, nanoparticles of the conjugates, as well as modified nanoparticles having PEGylated exteriors or encapsulated by red blood cell vesicles. The conjugates, nanoparticles and nanocarriers are useful for treating cancers and other diseases, as well as for imaging diseased tissue or organs.

The present invention relates to a phage or a composition that comprises it, wherein said phage expresses at least one specific recognition element and is furthermore conjugated with at least 300 molecules of a sonosensitiser. The invention further relates to the use of said phage in a sonodynamic therapy.

Methods of treating tumors by administering compounds to a patient are provided. Compounds such as pro drugs, e.g., 5-aminolevulinic acid (5-ALA), 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 invention relates to methods of sonodynamic therapy comprising the co-administration of a microbubble-chemotherapeutic agent complex together with a microbubble-sonosensitiser complex. It further relates to pharmaceutical compositions comprising these complexes and their use in methods of sonodynamic therapy and/or sonodynamic diagnosis. Such methods find particular use in the treatment of cancer, e.g. pancreatic cancer.

The present invention provides methods for preparing acoustically-sensitive microbubbles. The method includes the steps of: i) preparing a first surfactant solution comprising a first micelle-forming surfactant at a concentration above the critical micelle concentration (CMC); ii) adding one or more pharmaceutical compounds in a solvent to the first surfactant solution, thereby loading the micelles with the one or more pharmaceutical compounds; iii) preparing a second surfactant solution comprising a second surfactant, wherein the second surfactant comprises one or more matrix forming surfactants; iv) adding heat to the second surfactant solution to melt the surfactant and allowing the mixture to cool under rapid stirring; v) combining the second surfactant solution with the loaded micelles; vi) purging the surfactant mixture with a purging gas; vii) agitating the purged mixture under a constant stream of the purging gas; and, viii) separating the formed microbubbles by size.

Lipid formulation particularly for preparing stable gas-filled microvesicles, comprising distearoyl-phosphatidylcholine (DSPC), dipalmitoylphosphatidylethanolamine-PEG5000 (DPPE-PEG5000) and palmitic acid in an advantageous relative molar ratio. The formulation is useful in particular for therapeutic application with ultrasounds.

A microbubble composition, comprising: a plurality of microbubbles, a microbubble comprising a noble gas and/or perfluorocarbon encapsulated within a shell that comprises one or more of a lipid, a protein, or a polymer, and a microbubble optionally defining a cross-sectional dimension in the range of from about 0.5 to about 20 micrometers. A method, comprising forming a composition according to the present disclosure. A method, comprising administering a microbubble composition according to the present disclosure to a subject, the composition optionally comprising echogenic phospholipid microbubbles. A method, comprising: (a) identifying, with the application of energy, the location of a microbubble composition according to the present disclosure, the energy optionally being ultrasound, (b) controllably effecting rupture of microbubbles of a microbubble composition of the present disclosure, the rupture optionally being effected by application of ultrasound, or both (a) and (b).

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.

This invention related to manufactured microbubbles, as well as methods of using manufactured microbubbles, for example, in medicinal applications. The invention pertains to the physical structure and materials of the microbubbles, as well as to methods for manufacturing microbubbles, methods for targeting microbubbles for specific medicinal applications, and methods for delivering microbubbles in medical treatment.