Compounds are described which include polyvalent ligands linked to a cyclodextrin scaffold which exhibit strong binding affinities for lanthanides and favorable characteristics with respect to altering the relaxation time of coordinated water molecules. The compounds are useful as contrast agents in applications such as magnetic resonance imaging. The polyvalent ligands are also useful in applications requiring chelation of metal ions in other applications such as water treatment, sequestration of metal ions and treatment of diseases or conditions caused by exposure to toxic or radioactive metal ions.

Compositions comprising clathrin nanoparticles and methods for treating neurological-associated disorders.

A liposomal composition (“ADx-001”) is provided, ADx-001 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand. The macrocyclic gadolinium-based imaging agent may be conjugated to a fourth phospholipid.

An environmentally sensitive membrane binding polypeptide, pH (low)-sensitive membrane peptide (pHLIP) has improved insertion kinetics balanced with solubility to selectively target acidic tissues.

The present disclosure relates to a liquid pharmaceutical formulation comprising a DOSA-derived tetra-chelate of formula (I), in which M is an ion of a paramagnetic metal, preferably a Gd.sup.3+ ion, and R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined in the claims, in a pharmaceutical acceptable solvent. The present disclosure also relates to a method of preparation of said liquid pharmaceutical formulation and to a method of imaging involving said liquid pharmaceutical formulation.

A fusogenic liposome comprising a detectable agent and optionally a cytotoxic drug in its internal aqueous compartment or bound to the liposome membrane is provided, wherein said fusogenic liposome comprises a lipid bilayer comprising a plurality of lipid molecules having 14 to 24 carbon atoms, and at least one of said lipid molecules further comprises a cationic group, a cationic natural or synthetic polymer, a cationic amino sugar, a cationic polyamino acid or an amphiphilic cancer-cell binding peptide; and at least one of said lipid molecules further comprises a stabilizing moiety selected from the group consisting of polyethylene glycol (PEG), polypropylene glycol, polyvinyl alcohol, polyvinylpyrrolidone (PVP), dextran, a polyamino acid, methyl-polyoxazoline, polyglycerol, poly(acryloyl morpholine), and polyacrylamide. Methods utilizing these liposomes in treatment of cancer are further provided.

An imaging nanoparticle comprising a plant virus particle having an interior surface and an exterior surface, an imaging agent that is linked to the interior and/or exterior surface, and a layer of biocompatible mineral such as silica coated over the exterior surface, is described. The imaging nanoparticle can be used in method of generating an image of a tissue region of a subject, by administering to the subject a diagnostically effective amount of an imaging nanoparticle and generating an image of the tissue region of the subject to which the imaging nanoparticle has been distributed.

The invention provides a (drug-containing) lipid nanoparticle with: (i) at least one phospholipid; (ii) at least one lysolipid; and (iii) at least one phospholipid comprising a hydrophilic polymer; and (iv) at least one structural lipid of formula (I) which has the following general structure: ##STR00001## wherein R and R′ are long hydrocarbyl hydrophobic chains, Y is a linker element, and PHG is a polar head group described as large according to its van der Waals radius, and which is different from the phospholipid (i). The lipid nanoparticle can release a drug (or API) from within the lipid nanoparticle as a result of focused ultrasound (FUS) applied continuously, at least twice, to a desired part of the body to induce hyperthermia (an increase in temperature). FUS is applied after the lipid nanoparticle containing the drug has been administered to the live subject, and causes controlled release of the drug at the desired site of the body. Ultrasound is then halted, and the site of interest allowed to cool. Ultrasound is then applied again. Lipid nanoparticles can be labelled (for MRI, NIRF imaging), enabling real time monitoring of the drug in the human body. Imaging information can be used to direct and guide the nature of the FUS applied to the site of interest.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: ##STR00001##
wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or ##STR00002##
A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula:

##STR00001##

or a salt therof. R.sub.1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R.sub.2 is —N.sup.+H.sub.3, —N.sup.+H.sub.2Z, —N.sup.+HZ.sub.2, or —N.sup.+Z.sub.3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.