Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles.

Unlabelled: A PET tracer is desired to help guide the discovery and development of disease-modifying therapeutics for neurodegenerative diseases characterized by neurofibrillary tangles (NFTs), the predominant tau pathology in Alzheimer disease (AD). We describe the preclinical characterization of the NFT PET tracer F-MK-6240.

Methods: In vitro binding studies were conducted with H-MK-6240 in tissue slices and homogenates from cognitively normal and AD human brain donors to evaluate tracer affinity and selectivity for NFTs.

Discovery of 6-(Fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18)F]-MK-6240): A Positron Emission Tomography (PET) Imaging Agent for Quantification of Neurofibrillary Tangles (NFTs).

Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery of new disease modifying therapeutics targeting tau pathology. Herein, we present the discovery of 6-(fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine, 6 ([(18)F]-MK-6240), as a novel PET tracer for detecting NFTs.

Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy.

Chemoradiotherapy is a well-established treatment paradigm in oncology. There has been strong interest in identifying strategies to further improve its therapeutic index. An innovative strategy is to utilize nanoparticle (NP) chemotherapeutics in chemoradiation.

Coercing bisphosphonates to kill cancer cells with nanoscale coordination polymers.

Nanoscale coordination polymers containing exceptionally high loadings of bisphosphonates were coated with single lipid bilayers to control the drug release kinetics and functionalized with a targeting ligand to endow cell-targeting capability, leading to much enhanced cytotoxicity against human lung and pancreatic cancer cells.

Mesoporous Silica Nanoparticles with Co-Condensed Gadolinium Chelates for Multimodal Imaging.

Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd complexes at very high loadings (15.5-28.8 wt %).

Mesoporous Silica Nanoparticles with Co-Condensed Gadolinium Chelates for Multimodal Imaging.

Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd complexes at very high loadings (15.5-28.8 wt %).

Multifunctional mesoporous silica nanospheres with cleavable Gd(III) chelates as MRI contrast agents: synthesis, characterization, target-specificity, and renal clearance.

Mesoporous silica nanospheres (MSNs) are a promising material for magnetic resonance imaging (MRI) contrast agents. In this paper multifunctional MSNs with cleavable Gd(III) chelates are synthesized and characterized, and their applicability as MRI contrast agents is demonstrated both in vitro and in vivo. The MSNs contain Gd(III) chelates that are covalently linked via a redox-responsive disulfide moiety.

Two-electron oxidation of deoxyguanosine by a Ru(III) complex without involving oxygen molecules through disproportionation.

Among the many mechanisms for the oxidation of guanine derivatives (G) assisted by transition metals, Ru(III) and Pt(IV) metal ions share basically the same principle. Both Ru(III)- and Pt(IV)-bound G have highly positively polarized C8-H's that are susceptible to deprotonation by OH(-), and both undergo two-electron redox reactions. The main difference is that, unlike Pt(IV), Ru(III) is thought to require O(2) to undergo such a reaction.

Nanoscale metal-organic frameworks for biomedical imaging and drug delivery.

Metal-organic frameworks (MOFs), a class of hybrid materials formed by the self-assembly of polydentate bridging ligands and metal-connecting points, have been studied for a variety of applications. Recently, these materials have been scaled down to nanometer sizes, and this Account details the development of nanoscale metal-organic frameworks (NMOFs) for biomedical applications. NMOFs possess several potential advantages over conventional nanomedicines such as their structural and chemical diversity, their high loading capacity, and their intrinsic biodegradability.

Hybrid nanomaterials for biomedical applications.

Hybrid nanomaterials, composed of both inorganic and organic components, have recently been examined as promising platforms for imaging and therapeutic applications. This unique class of nanomaterials can not only retain beneficial features of both the inorganic and organic components, but also provides the ability to systematically tune the properties of the hybrid material through the combination of functional components. This feature article will summarize recent advances in the design and synthesis of hybrid nanomaterials and their applications in biological and biomedical areas.

Metal-organic frameworks as potential drug carriers.

Nanoparticle-based therapeutics have received increasing attention, as these systems can alleviate many drawbacks of conventional therapy. Metal-organic frameworks (MOFs), a new class of hybrid materials composed of metal ions and organic bridging ligands, have emerged as a promising platform for drug delivery, owing to their high drug loadings, biodegradability, and versatile functionality. The bulk MOF materials can absorb and release large amounts of therapeutics including ibuprofen, procainamide, and nitric oxide.

Postsynthetic modifications of iron-carboxylate nanoscale metal-organic frameworks for imaging and drug delivery.

Fe(III)-carboxylate nanoscale metal-organic frameworks (NMOFs) with the MIL-101 structure were synthesized using a solvothermal technique with microwave heating. The approximately 200 nm particles were characterized using a variety of methods, including SEM, PXRD, nitrogen adsorption measurements, TGA, and EDX. By replacing a percentage of the bridging ligand (terephthalic acid) with 2-amino terephthalic acid, amine groups were incorporated into the framework to provide sites for covalent attachment of biologically relevant cargoes while still maintaining the MIL-101 structure.