Cationic polymers having one or more anionic ligand end groups, including a new class of carboxylated branched poly(beta-amino ester)s that can self-assemble into nanoparticles for efficient intracellular delivery of different biomolecules, including a variety of proteins is disclosed.

Disclosed herein are bilayered substrates useful for treating infection and/or inflammation in a subject such as, for example, the upper respiratory system. In another aspect, the layers of the substrates disclosed herein include biocompatible and biodegradable polymers as well as one or more bioactive agents useful for treating infection and/or inflammation. In a further aspect, the layers of the substrate can contain nanoparticles incorporating the bioactive agents. In any one of the above aspects, the bioactive agents are released at a constant rate over a period of time. In still another aspect, the substrates disclosed herein are useful for reducing the mass of biofilms and reducing or preventing inflammation by inhibiting the production of interleukin-8.

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.

Provided are methods for treating a disease, disorder, or condition associated with an acid ceramidase (AC) biological activity. The methods include administering to a subject in need thereof a composition including an AC inhibitor and at least one additional active agent, such as a C6-ceramide nanoliposome (CNL); an inhibitor of a Bcl-2 family protein; a hypomethylating agent; an intensive chemotherapeutic agent such as cytarabine (AraC) and/or daunorubicin; a Hedgehog pathway inhibitor; a targeted agent, such as a FLT2 inhibitor or a EDH1/2 inhibitor; and/or an antibody drug conjugate that targets, for example, CD-33. The composition can include N-[(2S,3R)-1,3-dihydroxyoctadecan-2-yl]2-chloroacetamide (SACLAC) or a pharmaceutically acceptable salt thereof and at least one additional active agent. The disease, disorder, or condition associated with the AC biological activity can be a cancer, such as acute myeloid leukemia (AML).

The present disclosure provides a nanoparticle, a preparation process thereof, a method for treating cancer, a method for enhancing effect of a liver cancer drug, a method for ameliorating tumor hypoxia, and a method for enhancing effect of a liver cancer vaccine by using the nanoparticle.

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.

The present invention provides compositions comprising tolerizing immune modified particles (TIMPs) and methods for using and making said TIMPs. In particular, carrier polymer is covalently conjugated with antigenic peptide before particle formation, which allows for exquisite control of particle size and antigen encapsulation (e.g., for use in eliciting induction of immunological tolerance).

Conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to an HSP90 targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.

Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.

A novel and innovative method of fabricating nanoparticles with reproducible characteristics from batch-to-batch and during scale-up. The method is a dipolymerization-precipitation reaction facilitated by the inverse electron demand Diels-Alder (IEDDA) reaction.