The present invention provides a non-invasive near-infrared light-controlled nanomaterial for the treatment of diabetes and use of an upconversion fluorescent nanomaterial in the preparation of a tool for the treatment of diabetes, wherein the upconversion fluorescent nanomaterial includes an inorganic nanomaterial doped with rare earth elements, and a layer of water-soluble polymer and molecules targeting liver cells, which is on the surface of the nanomaterial. In the treatment of diabetes, there is no need to surgically implant invasive optical fibers in animals, and the upconversion nanomaterial in an organism is excited by near-infrared light with high tissue penetrability. The upconversion material converts the light of near-infrared band into visible light, to activate light-sensitive proteins. This enables the remote control of intracellular glucose metabolism-related signaling pathways independent of insulin with high temporal-spatial resolution, to promote the glycogen synthesis, inhibit the gluconeogenesis, and lower the blood glucose level.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether has the formula: ##STR00001##
wherein R.sub.1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days, or wherein R.sub.1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R.sub.2 is —N.sup.+(CH.sub.3).sub.3.

The current invention relates to a combination therapy comprising administering the antimitotic agent ABT-751 to a subject and delivering ionizing radiation to the same subject for the treatment of a brain tumor. Provided is for ABT-751 and ionizing radiation for use in such treatments.

Methods and systems for radiation therapy involve administering a payload / combination of biocompatible high-Z and semiconductor NPs to tissue, such as a tumor or an eye. Ionizing radiation may be directed towards the payload, and ionized electrons generate Cerenkov radiation (CR). The CR interacts with semiconductor NPs to produce chemical species that are damaging to cells. The payload may be administered via injection or via a radiotherapy (RT) device that includes NPs in a biodegradable polymer matrix. Biodegradation of the polymer matrix, which results in release of its payload, may be remotely activated using, for example, electromagnetic or sound waves. The payload may include one or more immunologic adjuvants capable of promoting an immunologic response at remote sites (such as a metastatic tumors) that are separate from the site at which the NPs and adjuvants were administered.

Disclosed is a method for increasing susceptibility of cancer cells to ionizing radiation by delivering to the cells a radiosensitizing agent that has one of the following properties: it perturbs the process of chromosome segregation thereby increasing chromosome missegregation; or (b) it is an inhibitor of an agent that promotes faithful chromosome segregation induces numeric chromosome instability in said cells and this instability is induced substantially simultaneously with or closely prior to or closely after irradiating the cells. Examples of such radiosensitizing agent include inhibitors of one or more of the following: Kif2b, MCAK, MPS1, Eg5/Kinesin-5 5, Polo-like kinase 4, MCAK, Bub1 and Hec1. Such agents specifically target proteins involved in maintaining or promoting faithful chromosome segregation.

The invention relates to novel biocompatible hybrid nanoparticles of very small size, useful in particular for diagnostics and/or therapy.

The purpose of the invention is to offer novel nanoparticles which are useful in particular as contrast agents in imaging (e.g. MRD and/or in other diagnostic techniques and/or as therapeutic agents, which give better performance than the known nanoparticles of the same type and which combine both a small size (for example less than 20 nm) and a high loading with metals (e.g. rare earths), in particular so as to have, in imaging (e.g. MRI), strong intensification and a correct response (increased relaxivity) at high frequencies.

Thus, the nanoparticles according to the invention, with diameter d.sub.1 between 1 and 20 nm, each comprise a polyorganosiloxane (POS) matrix including gadolinium cations optionally associated with doping cations; a chelating graft C.sup.1 DTPABA (diethylenetriaminepentaacetic acid bisanhydride) bound to the POS matrix by an —Si—C— covalent bond, and present in sufficient quantity to be able to complex all the gadolinium cations; and optionally another functionalizing graft Gf* bound to the POS matrix by an —Si—C— covalent bond (where Gf* can be derived from a hydrophilic compound (PEG); from a compound having an active ingredient PA1; from a targeting compound; from a luminescent compound (fluorescein).

The method for the production of these nanoparticles and the applications thereof in imaging and in therapy also form part of the invention.

The present disclosure provides a nitric oxide hydrogel for promoting tumor vascular normalization and radiosensitization and a preparation method thereof. The hydrogel includes a gel-forming polypeptide for forming a hydrogel and a β-galactose-protected NO donor molecule, where the gel-forming polypeptide and the β-galactose-protected NO donor molecule are covalently linked. In the present disclosure, the preparation method has a low synthesis cost, and adopts daily essential amino acid of the human body as raw materials, showing desirable biocompatibility. The hydrogel acts as a NO reservoir for continuous NO delivery on demand, which significantly solves the problem of a short half-life of NO molecules. Most importantly, the hydrogel releases NO only under the catalysis of β-galactosidase (β-Gal), with a release amount precisely controlled by an enzyme concentration.

Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM, leading to widespread shutdown of vascular flow, hemorrhage, and necrosis. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and/or mTOR inhibitors.

A method for removing or controlling or quantifying the presence of aldehydes, in particular acetaldehyde, is described. Such a method is useful in prolonging the shelf life of a pharmaceutical product.

Methods for treating tumors by administering ionizing radiation and an immune modulator to a patient with cancer are disclosed. The methods provide the dual benefits of anti-tumor efficacy plus normal tissue protection when combining immune modulators with ionizing radiation to treat cancer patients. The methods described herein also allow for the classification of patients into groups for receiving optimized radiation treatment in combination with an immune modulator based on patient-specific biomarker signatures.