The disclosure provides nanoemulsion compositions and methods of making and using thereof to deliver a bioactive agent such as a nucleic acid to a subject. The nanoemulsion composition comprises a hydrophobic core based on inorganic nanoparticles in a lipid nanoparticle that allows imaging as well as delivering nucleic acids. Methods of using these particles for treatment and vaccination are also provided.

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.

The present invention relates to a superparamagnetic gold nanoparticle cluster-protein nanoparticle fusion body for magnetic resonance imaging and magnetic thermotherapy. According to the present invention, a superparamagnetic gold nanoparticle cluster-protein nanoparticle fusion body which has target directionality and a high density of ultrafine gold nanoparticles uniformly coupled to the surface of protein nanoparticles can be fabricated with neither a separate surface stabilization process nor a separate target directionality conferring process. Hence, the superparamagnetic gold nanoparticle cluster-protein nanoparticle fusion body according to the present invention is superior to conventional gold nanoparticles in terms of biocompatibility and has excellent target directionality as well as being identified to have a temperature elevation potential in an alternating magnetic field and a functionality as a T2-MRI contrast medium thanks to the superparamagnetism property of the ultrafine gold nanoparticles.

The present disclosure provides methods and systems for cell processing, including delivery of imaging agents into cells. The methods and systems may comprise the use of a microfluidic device. The microfluidic device may comprise a channel comprising a compressive element. The compressive element may be configured to reduce a volume of the cell and facilitate the formation of one or more transient pores in a cell membrane of the cell. The one or more pores may permit one or more imaging agents to enter the cell. Also provided are modified cells produced using the disclosed methods and systems and methods of imaging the modified cells in a subject.

The disclosure provides nanoemulsion compositions and methods of making and using thereof to deliver a bioactive agent such as a nucleic acid to a subject. Compositions of the disclosure include nucleic-acid lipid nanoparticle complexes encoding for viral RNA polymerase region and protein antigen. The nanoemulsion compositions of the disclosure comprises a hydrophobic core, optionally including inorganic nanoparticles in a lipid nanoparticle that allows imaging as well as delivering nucleic acids. Methods of using these particles for treatment and vaccination are also provided, including methods for administering to a subject a composition of the disclosure in an amount sufficient to generate an immune response.

A rod-shaped plant virus having an interior surface and an exterior surface, and at least one imaging agent that is linked to the interior and/or exterior surface is described. The rod-shaped viruses can be combined into larger spherical nanoparticles. A rod-shaped plant virus or spherical nanoparticles including an imaging agent can be used in a method of generating an image of a tissue region of a subject such as a tumor or atherosclerotic tissue by administering the virus particle to the subject and generating an image of the tissue region of the subject to which the virus particle has been distributed.

A process for the preparation of beads including a biocompatible hydrophobic polymer, a perfluorocarbon, polyvinylalcohol and optionally a metal compound, including the steps of: adding the perfluorocarbon and optionally the metal compound to a solution of the biocompatible hydrophobic polymer in a polar solvent to provide a first liquid mixture, adding the first liquid mixture to an aqueous solution of a biocompatible surfactant including polyvinylalcohol under sonication to obtain a second liquid mixture, a) maintaining the sonication of the second liquid mixture while cooling, b) evaporating the polar solvent from the second liquid mixture to obtain a suspension of beads including the biocompatible hydrophobic polymer, the perfluorocarbon and optionally the metal compound, c) separating the beads from the suspension and preparing a water suspension of the beads and d) freeze-drying the water suspension to obtain the beads, wherein the addition of the first liquid mixture to the biocompatible surfactant in step b) is performed within a period of at most 10 seconds, wherein the sonication in step b) and the sonication in step c) are performed directly into the liquid mixtures by for example a probe or flow sonicator at an amplitude of at least 120 μm for 0.01-10 minutes and wherein the weight ratio of the biocompatible surfactant to the biocompatible hydrophobic polymer is at least 3:1. Beads having close F—H2O interactions, which are suitable for imaging purposes.

The invention is directed to the field of gene therapy, i.e. gene delivery into target cells, tissue, organ and organism, and more particularly to gene delivery via viral vectors. The inventors showed that it is possible by chemical coupling to modulate the coupling of a ligand in the surface of the capsid of AAV, for example AAV2 and AAV3b. In particular, the present invention relates to a recombinant Adeno-Associated Virus (rAAV) vector particle having at least one primary amino group contained in the capsid proteins, chemically coupled with at least one ligand L, wherein coupling of said ligand L is implemented through a bond comprising a —CSNH— bond and an optionally substituted aromatic moiety. Particularly, the inventors tested the chemical coupling of mannose ligand on AAV2 for subretinally injection to rats. The present invention further relates to a method for chemically coupling an Adeno-Associated Virus (AAV) vector particle with at least one ligand L and to a Recombinant Adeno-Associated Virus (rAAV) vector particle obtained by said method as well as a pharmaceutical composition comprising it and their corresponding medical use.

A biocompatible magnetic material containing an iron oxide nanoparticle and one or more biocompatible polymers, each having formula (I) below, covalently bonded to the iron oxide nanoparticle:

##STR00001##

in which each of variables R, L, x, and y is defined herein, the biocompatible magnetic material contains 4-15% Fe(II) ions relative to the total iron ions. Also disclosed in a method of preparing the biocompatible magnetic material.