Abstract: The invention relates to microbubble complexes for use in methods of sonodynamic therapy which comprise a microbubble attached to or otherwise associated with one or more linking groups, each linking group being bound to at least one sonosensitising agent and at least one chemotherapeutic agent. It further relates to the microbubble complexes themselves and to pharmaceutical compositions which contain them. The invention is particularly suitable for the treatment of deep-sited tumors, in particular pancreatic cancer.

Abstract: The invention relates to a microbubble-chemotherapeutic agent complex comprising a microbubble carrying a combination of chemotherapeutic agents for use in a method of treating cancer in a patient, wherein said combination of chemotherapeutic agents comprises: (a) a 5-fluoropyrimidine or a derivative thereof; (b) irinotecan or a derivative thereof; and (c) a platinum-based chemotherapeutic agent or a derivative thereof; and wherein said method comprises simultaneous, separate or sequential administration of folinic acid or a derivative thereof. The invention is particularly suitable for use in the treatment of deep-sited tumours and associated metastatic disease, for example in the treatment of pancreatic cancer. The invention further relates to the microbubble- chemotherapeutic agent complexes themselves, to methods for their preparation and to pharmaceutical compositions which contain them, optionally in combination with folinic acid or a folinic acid derivative.

Abstract: The invention provides polymeric particles comprising a matrix of a biocompatible polymer and polyethylene imine, said matrix having incorporated therein an anionic or hydrophobic sonosensitiser and, optionally, an immunomodulatory agent and/or an imaging agent. Such particles find use in methods of sonodynamic therapy, in particular in methods of combined sonodynamic therapy and immunotherapy, for example in the treatment of cancer, metastasis or micrometastasis derived from cancer. The invention is particularly suitable for the treatment of deep-sited, hard to treat tumours such as pancreatic cancer.

Abstract: 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.

Abstract: The invention provides a method of preparing a microbubble covalently attached to at least one therapeutic agent which comprises: (i) providing a lipid (e.g. a phospholipid) capable of forming a microbubble; covalently linking at least one therapeutic agent to said lipid to produce a functionalised lipid; and preparing a microbubble from said functionalised lipid. Microbubble-therapeutic agent complexes which comprise a microbubble shell formed from a plurality of lipids (e.g. phospholipids) in which at least a proportion of the lipids are covalently linked to at least one therapeutic agent are also provided. Examples of therapeutic agents which may be attached to the microbubble include chemotherapeutic agents and sonosensitising agents. The complexes find use in methods of sonodynamic therapy and, in particular, in methods of combined sonodynamic therapy and chemotherapy.

Abstract: 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.

Abstract: The invention generally relates to sonodynamic therapy using microbubble-sonosensitiser complexes and, more specifically, to such therapy for the treatment of deeply-sited tumours and associated metastatic disease. In particular, the invention relates to a combination therapy in which sonodynamic treatment of deeply-sited tumours with microbubble-sonosensitiser complexes is combined with treatment using immune checkpoint inhibitors. It further relates to methods of sonodynamic therapy in which a sonodynamic-induced abscopal response modulates a systemic regression of metastatic disease. In such methods the abscopal response may be further enhanced by co-administration of an immune checkpoint inhibitor. The invention is particularly suitable for the treatment of pancreatic cancer (e.g. pancreatic ductal adenocarcinoma) and associated metastasis.

Abstract: The invention provides CaO2 nanoparticles having a pH-responsive coating for use in a method of adjuvant therapy of hypoxic tumour cells or tissues. The nanoparticles find particular use in enhancing cancer therapies that depend on oxygen to exert their effect, such as photodynamic therapy (PDT), sonodynamic therapy (SDT), and radiotherapy. The invention also provides pharmaceutical compositions containing the coated CaO2 nanoparticles, together with at least one photosensitiser, sonosensitiser, or radiosensitiser and, optionally, at least one pharmaceutical carrier or excipient.

Abstract: The invention relates to microbubble complexes for use in methods of sonodynamic therapy which comprise a microbubble attached to or otherwise associated with one or more linking groups, each linking group being bound to at least one sonosensitising agent and at least one chemotherapeutic agent. It further relates to the microbubble complexes themselves and to pharmaceutical compositions which contain them. The invention is particularly suitable for the treatment of deep-sited tumors, in particular pancreatic cancer.

Abstract: The invention provides CaO2 nanoparticles having a pH-responsive coating for use in a method of adjuvant therapy of hypoxic tumour cells or tissues. The nanoparticles find particular use in enhancing cancer therapies that depend on oxygen to exert their effect, such as photodynamic therapy (PDT), sonodynamic therapy (SDT), and radiotherapy. The invention also provides pharmaceutical compositions containing the coated CaO2 nanoparticles, together with at least one photosensitiser, sonosensitiser, or radiosensitiser and, optionally, at least one pharmaceutical carrier or excipient.

Abstract: 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.