The present disclosure provides branched poly(β-amino esters) (PBAEs) of Formula (I) made by reacting primary amines with diacrylates. Further provided herein are compositions comprising the polymers of Formula (I), and methods of using the compositions and polymers as described herein for the treatment of disease.

L-(R).sub.n   (I)

Embodiments of the present disclosure provide for magnetic particle conjugates, methods of making the magnetic particle conjugates, methods of using magnetic particle conjugates, micelles (also referred to as a “magnetic composite nanocarrier” (MCNC)), methods of making micelles, methods of using micelles, and the like.

Described herein are carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a nitroboronic boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing the nitroboronic acid to an environment external to the nanoparticle. Targeted versions of the described nanoparticles are also described, as are related compositions, methods and systems.

Disclosed are methods and related compositions for concomitantly, locally administering immunosuppressants and doses of therapeutic macromolecules for reducing Type I and Type IV hypersensitivity.

Disclosed are biodegradable nanocarriers that have a net positive surface charge and zeta potential between about +2 to about +20 mV. The positive surface charge of the nanocarriers is provided by peptides that are covalently attached to the surface of the nanocarriers. The nanocarriers may comprise a drug and may be administered for localized and sustained delivery of the drug.

The present disclosure relates method for forming polyplexes, which find use in gene therapy applications as safe and non-toxic nucleic acid transfection agents.

There are provided herein, inter alia, complexes, compositions and methods for the delivery of nucleic acid into a cell in vivo. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

Agents that inhibit CX3CL1 in endothelial cells to reduce or inhibit immunosuppression mechanisms that are co-opted by cancer cells to evade host immune system, and that reduce immunosuppression in context of therapies that target VEGF-dependent signaling, and methods of use thereof.

The present technology provides a nanoparticle comprising: the polysiloxanes comprise silyloxy subunits having the structure (I) as shown herein, wherein R.sup.a at each occurrence is independently selected from a bond to a Si of another polysiloxane chain or a C.sub.1-12 alkyl group; R.sup.i at each occurrence is independently selected from the group consisting of C.sub.1-12 alkyl and C.sub.2-12 alkenyl groups, optionally substituted with a substituent selected from the group consisting of halogen and NR.sup.1.sub.2, wherein each occurrence of R.sup.1 is independently selected from H or a C.sub.1-12 alkyl group, or two R.sup.1 groups, together with the N atom to which they are attached, form a pyrrolidine or piperidine ring; the crosslinks between polysiloxanes comprise disulfide linkages, the nanoparticle comprises an exterior surface comprising surface-modifying groups attached to and surrounding the silica network, wherein the surface-modifying groups comprise polyethylene glycol (PEG), polysarcosine, polyzwitterion, polycation, polyanion, or combinations of two or more thereof; and the nanoparticle has an average diameter of 15 nm to 200 nm. The nanoparticles herein may include biomolecules such as polynucleic acids, proteins, and complexes thereof, e.g., Cas9 RNP.

This application discloses the compositions comprising biologically active synthetic nanoparticle constructs and methods of use thereof to modify gene expression including transcriptional activation and transcriptional repression.