Nanobialys for MR Imaging and Drug Delivery:
Researchers at Washington University have developed nanobialys shaped nanoparticles constructed from amphiphilic polymer material. The nanoparticles self-assemble into an aqueous core surrounded by a hydrophilic outer portion, and they incorporate manganese to provide contrast in MR imaging that averts typical problems with radiation exposure or gadolinium toxicity. Nanobialys can simultaneously be used as drug delivery vehicles carrying a chemotherapeutic or other drug agent within the aqueous inner core.

Advantages:

• Ease of manufacturing due to self-assembly nature of nanoparticles
• Non-gadolinium based agent

Publication: J Am Chem Soc 130(29):9186-9187. Ligand-Directed Nanobialys as Theranostic Agent for Delivery and Manganese-Based Magnetic Resonance Imaging of Vascular Targets.

PCT Publication: WO 2009/049089 A1

NanoRay for CT, Dual-Energy, and Spectral CT imaging and Drug Delivery:
Researchers at Washington University have developed nanocolloids that can contain various metals to enhance spectral CT imaging. Nanocolloids are easily formed as a lipid outer core surrounding an oil-based inner core. Nanocolloids can be site-targeted and used to delivery drugs for therapeutic applications. The advantage of these particles is their ability to carry metals on the inside of the particle such that the metal does not dissociate from the particle to cause toxicity issues in the body.

Advantages:

• Quantifiable imaging results
• Use with multiple possible metals that create distinct and distinguishable features
• Non-gadolinium based agent

PCT Publication: WO 2009/049083 A1

Manganese nanocolloids for MR imaging and Drug Delivery:
Lipid encapsulated, high stable manganese-organic compounds are incorporated at high metal density for very sensitive TI weighted MR imaging. The particles are easily functionalized, highly stable, can deliver drug therapy, and easily -manufactured at scale under GLP.

Advantages:

• Sensitive detection in the low nanomolar region
• Non-gadolinium based agent
• Image based drug delivery

Publications: Sensitive and efficient detection of vascular targets with fibrin specific manganese nanocolloids. Chem Comm. 2009: (on-line)

PCT Publication: WO 2009/049083 A1

NanoPA – Gold-based nanocolloids for Photoacoustic Imaging and Drug Delivery:
Lipid encapsulated, high stable gold particle colloidal suspensions that tuned to the NIR for very sensitive PAT imaging. The particles are easily functionalized, highly stable, can deliver drug therapy, and scalable.

Advantages:

• Sensitive detection 10 to 15-fold beyond hemoglobin
• Ideal for noninvasive cardiovascular (carotid) and cancer (Breast,prostate, GI, and head and neck imaging
• Image based drug delivery

Publication: Molecular photoacoustic tomography with colloidal nanobeacons. Angew Chem Int Ed 2009 (on line)

PCT Publication: WO 2009/049083 A1

Colloidal Iron Oxide Nanoparticles (CION) for MR Imaging and Drug Delivery:
Lipid encapsulated ferromagnetic nanocolloid particles have been developed for use in T1 or T2* MR imaging or for use in magnetic particle imaging (MPI). The CION particles can be functionalized before or after the synthesis process to enable drug delivery and/or site-specific targeting, and drugs can be either embedded in the hydrophobic core or the outer lipid layer. Current imaging with iron oxide particles requires at least 24 hours before imaging, but site-targeted nanoparticles of this invention enable imaging within 1 hour of contrast agent delivery.

Advantages:

• Reduced time between injection and imaging
• Sensitive detection in the low nanomolar region
• Non-gadolinium based agent

PCT Publication: WO 2009/049083 A1

Universal Cationic Linker Peptides:
Researchers at Washington University have developed a peptide linker derived from the amphipathic cationic compound melittin that can be used to link various cargo types to pre-formed nanoparticles or living cells. The proprietary peptide composition can rapidly and stably insert into any nanoparticle with a lipid membrane or any cell type, but does not manifest the cytotoxic activity of the native peptide (melittin, a known pore former). The free end of the peptide linker can attach molecules for site-specific targeting, image detection and/or drug delivery. Studies have demonstrated that the linker peptide can be used to anchor targeting ligands and drug compounds to different nanoparticle types and cells and that such targeted drug delivery system can modulate anticipated pathways in target cells.

Advantages:

• Utility with any nanoparticle having an outer lipid layer or any cell type
• Ability to secure cargo post-nanoparticle synthesis
• Versatile linker can carry multiple cargo’s on one nanoparticle or cell
• Simple formulation with long-term stability

Phospholipid Prodrugs:
Researchers at Washington University have developed a lipid nanoparticle-based platform technology to create and prodrugs within the nanoparticle for direct drug delivery to the site of action. The prodrug is created by coupling the active pharmaceutical ingredient to a fatty acid to form a stable membrane complex. Transfer to the target cell membrane via a patented technique termed “contact facilitated drug delivery” allows enzymatic release of the drug within the cell membrane, allowing it to diffuse into the cell cytosol and or the nucleus.

Advantages:

• Drug delivery only after specific binding at target site
• Prodrug delivery for release of drug by enzyme action

File Number: 6819, 7543, 7545, 7570, 7663