Johns Hopkins University

University System of Maryland

Other

Graeme F Woodworth

Justin Scot Hanes

Jeffrey A Winkles

Anthony J Kim

Jung Soo Suk

Panagiotis Mastorakos

Clark Zhang

Aniket Wadajkar

Sven Oliver Muckenfuß

Elizabeth A Nance

Stephen Eckhof

Craig S Schneider

Metastatic triple negative breast cancer (TNBC) still carries a dismal prognosis with the current treatment paradigms. The effectiveness of drug treatment for many solid tumors such as TNBC is limited by tumor heterogeneity, lack of tumor specificity, off-target toxicities, and transient therapeutic action(s). Strategies that provide tumor-specific, sustained concentrations of drugs to the tumors and tumor receptor-specific binding, while reducing off-target effects are needed to ensure sufficient tumor cell uptake within the primary and metastatic tumor microenvironment. The decreased non-specific adhesivity, receptor-targeted nanoparticle formulations ('DART' nanoparticles) of the invention were assessed for clinical potential in directing biological agents to the cell surface receptor Fn14, which is expressed in many solid cancer types, including TNBC primary tumors and metastatic lesions. They are contemplated for use against solid tumors, particularly brain tumors such as glioblastoma and breast cancer, including metastatic breast cancer.

Decreased adhesivity receptor-targeted nanoparticles for Fn14-positive tumors

Provided are targeted structure-specific particulate-based delivery systems comprising: a nanoparticle; a PEG polymer coating on the surface of the nanoparticle; a targeting moiety conjugated on a surface of the nanoparticle and configured to promote specific binding to a cell surface molecule expressed by a target cell; and a biologically active agent in or on the nanoparticle, wherein the biologically active agent is selected to enhance a desired response in a target cell intracellularly or extracellularly. Methods of treating a disease or disorder administering the delivery system are contemplated.

Targeted structure-specific particulate delivery systems

A synthetic gene delivery platform with a dense surface coating of hydrophilic and neutrally charged PEG, capable of rapid diffusion and widespread distribution in brain tissue, and highly effective gene delivery to target cells therein has been developed. Nanoparticles including nucleic acids, are formed of a blend of biocompatible hydrophilic cationic polymers and they hydrophilic cationic polymer conjugated to hydrophilic neutrally charged polymers such as polyethylene glycol. The nanoparticles are coated with polyethylene glycol at a density that imparts a near neutral charge and optimizes rapid diffusion through the brain parenchyma. Methods of treating a disease or disorder of the brain including administering a therapeutically effective amount of nanoparticles densely coated with polyethylene glycol are also provided.

Engineering synthetic brain penetrating gene vectors

Non-adhesive particles as large as 110 nm can diffuse rapidly in the brain ECS, if coated with hydrophilic coatings such as PEG coatings and preferably having neutral surface charge. The ability to achieve brain penetration with larger particles will significantly improve drug and gene delivery within the CNS since larger particles offer higher drug payload, improved drug loading efficiency, and significantly longer drug release durations.

Rapid diffusion of large polymeric nanoparticles in the mammalian brain

Dynamic, rigid, and convertible dynamic-to-rigid devices and methods of using such devices to treat spinal instability conditions of the cervical spine are provided. The devices may include an interspinous, interlaminar stabilization device configured for interlaminar placement between the spinous processes of adjacent cervical vertebrae and optionally secured to the lamina using bone screws or crimped or rigidly fixed to the spinous process. Multiple devices may be used to enable treatment of multiple levels at the same time.

Interlaminar, interspinous stabilization devices for the cervical spine

Engineering synthethic brain penetrating gene vectors

Growing community of inventors

Baltimore, MD, United States of America

Graeme F Woodworth