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Extracellular Vesicles (EVs), including exosomes and microvesicles, are nanometer-sized membranous vesicles that can carry different types of cargos, such as proteins, nucleic acids and metabolites. EVs are produced and released by most cell types. They act as biological mediators for intercellular communication via delivery of their cargos. This unique ability spurred translational research interest for targeted delivery of therapeutic molecules to treat a wide range of diseases. EVs also contain interesting information of their specific cellular origin.

The Transforming Growth Factor Beta (TGF-ß) ligands (i.e., TGF-ß1, -ß2, -ß3) are key regulatory proteins in animal physiology. Disruption of normal TGF-ß signaling is associated with many diseases from cancer to fibrosis. In mice and humans, TGF-ß activates TGF-ß receptors (e.g., TGFBR1), which activates SMAD proteins that alter gene expression and contribute to tumorigenesis.  Reliable animal models are essential for the study of TGF-ß signaling.

The baculovirus-based protein expression system has gained increased prominence as a method for expressing recombinant proteins that are used in a wide range of biomedical applications. An important step in the use of this system is the ability to determine the virus infectious titer, i.e., the number of active baculovirus particles produced during an infection of the insect host cell.

Baculoviruses have been used for decades to produce proteins in insect cell hosts. Current systems for generating recombinant baculovirus have several shortcomings which prevent their easy use in high-throughput applications. 

Medical imaging is an important resource for early diagnostic, detection, and effective treatment of cancers. However, the screening and review processes for radiologists have been shown to overlook a certain percentage of potentially cancerous image features. Such review errors may result in misdiagnosis and failure to identify tumors. These errors result from human fallibility, fatigue, and from the complexity of visual search required.

Chronic leg ulcers are a debilitating vasculopathic complication for some patients with sickle cell disease (SCD). Prevalence of leg ulcers varies based on age and geographic location; about 5-10% of all SCD patients may suffer leg ulcers. These leg ulcers are painful, result in infections, hospitalization, disability, and negatively impact the patient’s social and psychological wellbeing on an ongoing basis.

Small molecule fluorescent probes are important tools in diagnostic medicine. Existing far-red and near-IR cyanine fluorophores (e.g. Cy5, Alexa 647, Cy7, ICG) are active in the far-red and near-range, but these agents suffer from modest quantum yields (brightness) which limit wide utility. It has been reported that the limited brightness of these fluorophores is due to an excited-state C-C rotation pathway.

In collaboration with surgery specialists from Johns Hopkins University, researchers at the National Cancer Institute (NCI) developed novel hydrogel compositions and methods of using them in the microsurgical suturing of blood vessels, which is particularly beneficial for surgeons in whole tissue transplant procedures. The lead candidate electropositive hydrogels, called APC1, was demonstrated in anastomosis mice models to be well tolerated, biocompatible, and non-toxic.

Studies have shown that Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) suppresses tumor growth and tumor-associated angiogenesis. Currently, the main obstacle in using TIMP-2 as a biologic therapeutic has been the inability to produce sufficient quantities of the protein for testing and development. 

The invention relates to novel lipid-based nanoparticles (liposomes) for use in targeted, on demand and on site drug delivery. The particles include a wall surrounding a cavity, wherein the wall is comprised of:

1. A lipid bilayer comprising 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC_8,9PC), dipalmitoylphosphatidylcholine (DPPC), and 1,2-distearoyl-sn-glycero-3-

phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), and