Disclosed are nanoparticles comprising a polymer carrier formed from a poly(ethylene glycol) and a poly(carbonate) copolymer which encapsulates a cargo entity such as an ERK inhibitor and/or chemotherapeutic agent. Therapeutic uses of the nanoparticles are also described, including methods of treating a cancer such as pancreatic cancer.

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.

The present disclosure relates to methods and compositions comprising derivatized-chitosan polyplexes reversibly coated with a polyanion-containing block co-polymer for the localized expression of IL-12 in mucosal tissues, preferably in combination with an IFN-1 activator/inducer, for use in cancer immunotherapy.

Mucus penetrating nanoparticles for inducing, increasing, or enhancing an immune response typically include core of a blend of a biodegradable hydrophobic polymer and a hydrophilic polymer, wherein ≥50% of the biodegradable polymer is conjugated to the hydrophilic polymer, and the hydrophilic polymers forms a coating on the particle. The particles encapsulate a cargo, typically an antigen, adjuvant or other immunomodulator, or a nucleic acid encoding the antigen, or combination thereof. Pharmaceutical compositions including an effective amount of particles to induce an immune response in a subject in need thereof are also provided. Methods of inducing an immune response are also provided, and typically include administering to a subject, preferably via the respiratory tract, the pharmaceutical composition. In some embodiments, the subject has cancer or an infection of the lung.

From diagnostic imaging to drug delivery, nanoparticles have found a tremendous variety of uses across fields. Often, when designing these nanoscale constructs, the two most important criteria are particle size and core loading. For example, small particles below 100 nm can have many advantages for drug delivery—including improved specificity to tumors through the enhanced permeability and retention (EPR) effect. Likewise, higher loading nanoparticles translate very well to more effective drug delivery and cancer imaging—allowing for lower dosage and reduced costs. Traditional formulations of nanoparticles using drug absorption or precipitation methods generally struggle to obtain >50% loading. Disclosed herein is a precipitation process allowing for production of stable particles at very high core loading by taking advantage of different time scales while maintaining biologically relevant sizes. New mixing designs allow for the separation of the precipitation and stabilization steps to generate these high loading nanoparticles.

The present invention relates to a polymer composite for ultrasound-based cancer immunotherapy, which comprises an peroxalate derivatives, and a preparation method thereof. The polymer composite according to the present invention is a structure in which the peroxalate derivatives are encapsulated in an amphipathic polymer compound in which a biocompatible polymer and a sonosensitizer are combined. The peroxalate derivatives produce free electrons and carbon dioxide (CO.sub.2) by reaction with a high concentration of hydrogen peroxide (H.sub.2O.sub.2) in cancer tissue, the generated electrons raise the energy level of the sonosensitizer in the polymer composite to increase the amount of reactive oxygen species (ROS) production, thereby exhibiting an effect of increasing the death rate of cancer cells. In addition, by ultrasound treatment, immunogenic cell death (ICD) is induced due to the cavitation effect of the produced CO.sub.2, so molecules capable of activating immune cells in cancer cells are released without damage to induce an immune response to cancer. Therefore, the polymer composite according to the present invention is expected to be effectively used as an ultrasound-based cancer immunotherapeutic agent.

Disclosed are methods for treating muscular diseases that involve the use of a nicotinamide adenine dinucleotide (NAD) activator.

Provided herein are nanoparticle compositions (e.g., nanoparticle compositions comprising high atomic number ions) that are useful for imaging diseases in a subject as well as radiosensitizing a disease in a subject (e.g., radiosensitizing a cancer in the subject). Methods of imaging a subject, methods of treating cancer, and processes of preparing the nanoparticle compositions are also provided.

The invention provides methods of making microparticle and nanoparticle ocular implants from a compositions comprising: 99 to 60% (w/w) of a photopolymerizable composition selected from the group of fragments or monomers consisting of polyalkylene glycol diacrylate and polyalkylene glycol dimethacrylate, wherein the photopolymerizable composition has a molecular weight in the range of 100 to 20,000 Dalton; a biodegradable polymer selected from the group consisting of aliphatic polyester-based polyurethanes, polylactides, polycaprolactones, polyorthoesters and mixtures, copolymers, and block copolymers thereof; a photoinitiator; and a therapeutic agent.