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 MRI contrast composition includes a liposome and a europium metal complex disposed within the liposome. The europium metal complex includes a europium metal ion and a multi-dentate ligand selected from the group consisting of cryptands and thiacryptands and one or more counter-ions that balances a charge of the europium metal ion and the multi-dentate ligand, the europium metal ion being switchable between a 2÷ and 3÷ oxidation state. The contrast composition advantageously provides an oxidation-responsive dual-mode contrast agent because it would enhance either T.sub.1-weighted images or CEST images depending on the oxidation state of Eu.

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.

Phospholipid-polymer-aromatic conjugates comprising binding ligands, liposome compositions including the phospholipid-polymer-aromatic conjugates, and binding ligands having an affinity for misfolded proteins are described. The phospholipid-polymer-aromatic conjugate may be represented by Structural Formula I: PL-AL-HP-X-BL (I). In Formula I, PL is a phospholipid, AL is an aliphatic linkage, HP is hydrophilic polymer, X is a link between the phospholipid-polymer and the binding ligand, and BL is polycyclic aromatic compound that functions as a binding ligand. The liposomal compositions may be useful for the imaging of misfolded and/or aggregated proteins.

The present disclosure provides imaging and contrast agents, and methods of using the agents. According to some embodiments of the disclosure, agents and methods for magnetic resonance imaging and related technologies are provided.

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.

Disclosed herein are novel synthetic polypeptides and uses thereof in the preparation of liposomes. According to embodiments of the present disclosure, the synthetic polypeptide comprises a membrane lytic motif, a masking motif, and a linker configured to link the membrane lytic motif and the masking motif. The linker is cleavable by a stimulus, such as, light, protease, or phosphatase. Once being coupled to a liposome, the exposure to the stimulus cleaves the linker that results in the separation of the masking motif from the membrane lytic motif, which in turn exerts membrane lytic activity on the liposome that leads to the collapse of the intact structure of the liposome, and releases the agent encapsulated in the liposome to the target site. Also disclosed herein are methods of diagnosing or treating a disease in a subject by use of the present liposomes.

An in-case stand for a musical instrument that supports a musical instrument in the open musical instrument case, such as a guitar, in an inclined position making the headstock and the neck readily accessible for string changes, cleaning or light maintenance.

Provided are aromatic compounds, phospholipid-polymer-aromatic conjugates comprising the aromatic compounds, and liposome compositions including the phospholipid-polymer-aromatic conjugates. The liposomal compositions may be useful for imaging of Alzheimer's Disease, for example, imaging of the amyloid-β plaque deposits characteristic of Alzheimer's Disease.