The present invention provides a hydrogel for comprising a biodegradable polyphosphazene polymer, a radiation-sensitive diselenide cross-linker; and one or more payloads releasably loaded within the hydrogel. The present invention further provides methods for radiosensitizing target tissues such as tumors and providing sustained delivery of therapeutics triggered by irradiation. In another aspect, the present invention provides a method that includes: introducing the hydrogel, as describes herein, adjacent to malignant or marginal tissue; and administering radiation to the hydrogel, thereby disrupting the selenocystamine cross-linkers and releasing the one or more payloads.

Reactive oxygen species (ROS) generated with noninvasive ultrasound and sonosensitizers, potently synergize with selected immunomodulators to hyperactivate dendritic cells and macrophages at desired locations and times within the body. Together with the tumor antigens provided by dying/dead tumor cells, these signals can result in activation of adaptive immune responses. This approach is useful for eliciting T cell responses within tumors present in any tissue of the body.

Disclosed are methods of obtaining zero vergence ultrasound waves for providing sonodynamic therapy with ultrasound waves. The method includes coupling a sonodynamic therapy device with an array of flat piezoelectric transducers to a skin surface. A controller is configured to generate an electrical drive signal at a frequency, modulate the drive signal, and drive the transducer with the modulated drive signal at the frequency to produce a zero vergence ultrasound wave to produce an average acoustic intensity sufficient to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.

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.

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.

The present invention relates to a sensitizer-peptide conjugate for use in the treatment of cancer. In particular, the present invention relates to a sensitizer-peptide conjugate for use in the treatment of melanoma. The use of such sensitizer-peptide conjugate in photodynamic therapy or sonodynamic therapy is also disclosed. According to the present invention, there is provided a sensitizer-peptide conjugate for use in the treatment of cancer; wherein the sensitizer-peptide conjugate comprises at least one sensitizer and at least one peptide.

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.

The present invention provides amphiphilic telodendrimers that aggregate to form nanocarriers characterized by a hydrophobic core and a hydrophilic exterior. The nanocarrier core may include amphiphilic functionality such as cholic acid or cholic acid derivatives, and the exterior may include branched or linear poly(ethylene glycol) segments. Nanocarrier cargo such as hydrophobic drugs and other materials may be sequester in the core via non-covalent means or may be covalently bound to the telodendrimer building blocks. Telodendrimer structure may be tailored to alter loading properties, interactions with materials such as biological membranes, and other characteristics.

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.

Disclosed are methods of producing randomized 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.