Disclosed herein is a particle containing an inner liposomal vesicle (ILV) encapsulating a therapeutic agent; an outer liposomal vesicle (OLV) encapsulating the ILV; a membrane fusion-promoting agent; and a pH-altering agent. Also disclosed are methods of delivering a therapeutic agent to a subject comprising: a) providing a herein disclosed particle b) triggering ILV and OLV fusion; and c) releasing the therapeutic agent outside of the OLV. Also disclosed are methods for treating a disease in a subject in need thereof comprising: administering to a subject a herein disclosed particle. Also disclosed are methods to release insulin to an environment comprising increased glucose levels, the method comprising exposing to the environment a herein disclosed particle.

Described herein are liposome-based nanocarriers that selectively target bone marrow, minimize tumor delivery, and maintain high drug concentrations in bone marrow when compared to conventional systemic delivery. The composition of the liposome-based nanocarriers may also be tuned to selectively target lymph nodes and other reticuloendothelial system organs (e.g., spleen, e.g., liver). Also described herein are methods of imaging and mapping the bone marrow and/or other reticuloendothelial system organs using the described liposome-based nanocarriers. These methods provide high resolution non-invasive and quantitative imaging via PET, which offers advantages over conventional imaging/tracking methods. Furthermore, in certain embodiments, the liposome-based carriers are used to stabilize and deliver radioprotectant/free radical scavenger drugs to the bone marrow, thereby protecting the bone marrow from subsequent radiation exposure, thereby limiting the adverse impact of radiation exposure on the individual.

The present disclosure relates to compositions and methods for enhancing T cell response in vivo. For example, a method of enhancing T cell response in a subject or treating a subject having cancer, the method comprising: administering an effective amount of a composition comprising modified cells to the subject having a form of cancer associated with or expressing an antigen, for example, a solid tumor antigen; and administering (1) a nucleic acid encoding the antigen, (2) additional modified cells comprising the nucleic acid or the antigen, or (3) microorganisms, for example cold viruses, comprising the nucleic acid or the antigen. In embodiments, the modified cells comprise mixed cells targeting a solid tumor antigen and a white blood cell (WBC) antigen. In embodiments, the modified cells comprise a dominant negative form of an immune checkpoint molecule (e.g., PD-1). In embodiments, the modified cells comprise an exogenous polynucleotide encoding a therapeutic agent, such as IL-12 and IFNγ.

The present disclosure features compositions and methods for the treatment of bacterial infections, such as bacterial infections caused by bacterial cells residing within a host cell (e.g., a mammalian cell, e.g., immune cell, e.g., macrophage or dendritic cell). The compositions and methods include delivering antimicrobial agents to specifically target the intracellular compartment (endosome, phagosome, lysosome, or cytosol) in which the bacterial cell resides.

The present disclosure features compositions and methods for the treatment of bacterial infections, such as bacterial infections caused by bacterial cells residing within a host cell (e.g., a mammalian cell, e.g., immune cell, e.g., macrophage or dendritic cell). The compositions and methods include delivering antimicrobial agents to specifically target the intracellular compartment (endosome, phagosome, lysosome, or cytosol) in which the bacterial cell resides.

Many tumors induce and maintain an immunosuppressive tumor microenvironment (TME) that enables tumor to escape host immune system. The present disclosure identifies that cancer cells secrete exosome/microparticle-free, soluble, phosphorylated Hsp70 (pHsp70 (Heat Shock Protein 70 (Hsp70))), which triggers macrophage (M) M2 polarization. It is a further aspect that lipid nanovesicles (NVs) made of dioleoylphosphatidylglycerol (DOPG) and of DOPG complexed with saposin C (SapC) bind to cancer secreted Hsp70, inhibit M differentiation and polarization, and reduce tumor growth. In addition, administration of DOPG-NVs rendered monocytes insensitive to TLR2 (Toll Like Receptor 2) and TLR6 (Toll Like Receptor 6) ligands, suggesting that administration of DOPG-NVs interferes with TLR function.

Therapeutic methods and compositions for the in utero or postnatal treatment of diseases associated with alternative splicing are provided. Compositions of the disclosure include delivery nanoparticles with an inner region surrounded by a nucleic acid scaffolding that is, in turn, linked to therapeutic agents that promote healthy mRNA splicing phenotypes in fetal cells when the compositions are delivered to a fetus in utero or in a patient after birth. The nanoparticles preferably include targeting complexes or antibodies that promote endosomal uptake into such cells and escape peptides that release the nanoparticles from endosomes into the cytosol within the cells to allow the therapeutic agents to promote preferred splicing

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.

Dimer and monomer molecules according to general formulas (I) or (II) are useful as lipid switch molecules when incorporated into a membrane of a liposome.

##STR00001##

wherein R.sup.1 is a hydrophobic tail having at least 6 carbons and wherein R.sup.2 is selected from the group consisting of —NH.sub.2,

##STR00002##

wherein, for the dimer, the linker is a saturated carbon chain having 2 to 6 carbons or is a para-xylene linker; and when R.sup.2 is charged anions are present to render the charge neutral. These molecules can bind ATP or similar small phosphorylated molecules between R.sup.2 groups, which changes the shape of the molecule or the molecules orientation within the membrane thereby acting as a “switch” to release a therapeutic agent from the liposome.

A method of manufacturing an immunogenic composition forming a vaccine is disclosed. The method includes providing an antigen, providing a dry lipid blend, hydrating the dry lipid blend with an antigen solution, wherein the hydration is configured to form a colloidal vaccine solution, and extruding the colloidal vaccine solution, wherein the extrusion is configured to form a vaccine particle.