A hyperbranched polymer includes a hyperbranched, hydrophobic molecular core, respective low molecular weight polyethyleneimine chains attached to at least three branches of the hyperbranched, hydrophobic molecular core, and respective polyethylene glycol chains attached to at least two other branches of the hyperbranched, hydrophobic molecular core. Examples of the hyperbranched polymer may be used to form hyperbranched polyplexes, and may be included in DNA or RNA delivery systems.

The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides. Other aspects are generally directed to methods of making or using such particles, kits involving such particles, or the like.

This disclosure presents compositions comprising phosphocreatine and nanoparticles containing triiodothyronine (T3), and to their use in treatment of cardiac conditions, particularly cardiac arrest and acute heart failure, as well as conditions generally relating to hypoxia, such as ischemia and stroke.

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

The present invention relates to a nanoparticle comprising a nanomaterial and at least a first ligand and a second ligand tethered to the nanoparticle. The present invention further relates to a nanoparticle for use as a medicament or diagnostic agent. The present invention also relates to a nanoparticle for use in a method of preventing or treating a disease selected from diabetic nephropathy, glomerulonephritis, glomerular VEGF A dysregulation, endothelial VEGF A dysregulation, diabetic retinopathy, rheumatoid arthritis, age-related macular degeneration, and cancer such as breast cancer. Furthermore, the present invention relates to a method of preparing a nanoparticle.

The present invention relates to PCSK9 inhibitors and methods of use thereof. Specifically, the invention relates to PCSK9 cell-based assay, PCSK9 inhibiting polypeptides and derivatives thereof. The invention includes pharmaceutical compositions comprising a PCSK9 inhibitor polypeptide together with a pharmaceutically acceptable carrier and method for treating cardiovascular disorders, hyperlipidemia, inflammatory diseases or inflammatory response to infection.

Provided in the present invention is a bispecific antibody which comprises an anti-MUC1 VHH antibody fragment and an anti-CD16 VHH antibody fragment. The antibody fragment used in the present invention is a variable region sequence derived from a heavy chain camelid antibody and has a high binding affinity to the antigen. Antibody fragments recognizing MUC1 and CD16 are constructed in the same antibody molecule by the invention, so that the antibody molecule can specifically bind to MUC1 and CD16 molecules to promote the killing effect of NK cells on MUC1-positive expression cells and has an inhibiting effect on the growth of MUC1-positive tumors. Also provided is a conjugate of the bispecific antibodies, a related pharmaceutical composition and use.

Methods of treating subjects having G4C2 dipeptide repeat expansion in the gene C9ORF72, including subjects having amyotrophic lateral sclerosis or frontotemporal degeneration (ALS/FTD), are provided. Compounds directed at reducing the toxicity of G4C2 dipeptide repeat expansion in the gene C9ORF72 are described.

Particles with a spatial and/or temporal release profile for delivery of different agents at different times to the same cells of a subject have been developed. The particles include a core polymeric particle containing a polymer and a first agent, a tethering moiety, covalent linker or covalent linkage attached to the core particle, and a tethered particle attached to the particle via the tethering moiety, covalent linker or covalent linkage and containing a second agent, where the agents are released at different times within or to the same cells. The first and second agents may be a therapeutic or prophylactic agent, such as an antigen, an immunomodulator, an anti-neoplastic agent, a hormone, an inhibitor, etc. The particles may form compositions for treating diseases with a spatial and/or temporal treatment regimen.

Provided herein are compositions and methods for diagnosis and therapy through targeted nano-delivery to injured brain endothelium. In some aspects, the compositions comprise a population of polyester derived nanoparticles, wherein each polyester derived nanoparticle comprises a) a therapeutic agent encapsulated therein for treating traumatically injured, inflamed, diseased, or disrupted endothelial cells, and b) a targeting ligand bound to the nanoparticle, wherein the targeting ligand binds to a biomarker for the injured, inflamed, diseased, or disrupted endothelial cells, are provided. The nanoparticles can be used for targeting difficult-to-reach injury sites, including the blood brain barrier and brain tissue.