The University of Chicago

The University of North Carolina at Chapel Hill

Savannah River Nuclear Solutions, LLC

Wenbin Lin

Chunbai He

Demin Liu

Kuntal Manna

Pengfei Ji

Wenbo Han

Christopher Y Poon

Stephanie Kramer

Joseph Della Rocca

Christina Chan

Kuangda Lu

Kaiyuan Ni

Takahiro Sawano

Guangxu Lan

Kathryn M L Taylor-Pashow

Carter W Abney

Aiguo Hu

Helen L Ngo

Teng Zhang

Zekai Lin

Xuanyu Feng

Xiaopin Duan

Joseph M Falkowski

Stephanie A Kramer

Nanoparticles comprising micheliolide (MCL) or derivatives thereof, and optionally additional therapeutic agents, such as chemotherapeutic agents, are described. Also described are methods of treating diseases, such as cancer, comprising the use of combinations of MCL or a derivative thereof with X-ray irradiation and/or other therapeutic agents, such as immune checkpoint inhibitors. The use of the combinations can provide synergistic anticancer therapeutic efficacy, for example, as the MCL or derivative thereof can both sensitize cancer cells to therapy and target resistant cancer stem cells (CSCs) for selective cell death.

Combination of micheliolide derivatives or nanoparticles with ionizing radiation and checkpoint inhibitors for cancer therapy

Lewis acidic metal-organic framework (MOF) materials comprising triflate-coordinated metal nodes are described. The materials can be used as heterogenous catalysts in a wide range of organic group transformations, including Diels-Alder reactions, epoxide-ring opening reactions, Friedel-Crafts acylation reactions and alkene hydroalkoxylation reactions. The MOFs can also be prepared with metallated organic bridging ligands to provide heterogenous catalysts for tandem reactions and/or prepared as composites with support particles for use in columns of continuous flow reactor systems. Methods of preparing and using the MOF materials and their composites are also described.

Strongly Lewis acidic metal-organic frameworks for continuous flow catalysis

Metal-bisphosphonate nanoparticles are disclosed. Also disclosed are pharmaceutical compositions including the metal-bisphosphonate nanoparticles, methods of preparing the metal-bisphosphonate nanoparticles and materials comprising the nanoparticles, and methods of using the compositions to treat cancer or bone-related disorders (e.g., bone-resorption-related diseases, osteoporosis, Paget's disease, and bone metastases) and as imaging agents.

Metal bisphosphonate nanoparticles for anti-cancer therapy and imaging and for treating bone disorders

Metal-organic layers (MOLs) and metal-organic nanoplates (MOPs) comprising photosensitizers are described. The MOLs and MOPs can also include moieties capable of absorbing X-rays or other ionizing irradiation energy and/or scintillation. Optionally, the photo sensitizer or a derivative thereof can form a bridging ligand of the MOL or MOP. Also described are methods of using MOLs and MOPs in photodynamic therapy, X-ray induced photodynamic therapy (X-PDT), radiotherapy (RT), radiodynamic therapy, or in radiotherapy-radiodynamic therapy (RT-RDT), either with or without the co-administration of another therapeutic agent, such as a chemotherapeutic agent or an immunomodulator.

Nanoscale metal-organic layers and metal-organic nanoplates for x-ray induced photodynamic therapy, radiotherapy, radiodynamic therapy, chemotherapy, immunotherapy, and any combination thereof

Surface hydroxyl groups on porous and nonporous metal oxides, such as silica gel and alumina, were metalated with catalyst precursors, such as complexes of earth abundant metals (e.g., Fe, Co, Cr, Ni, Cu, Mn and Mg). The metalated metal oxide catalysts provide a versatile family of recyclable and reusable single-site solid catalysts for catalyzing a variety of organic transformations. The catalysts can also be integrated into a flow reactor or a supercritical fluid reactor.

Metal oxide-supported earth-abundant metal catalysts for highly efficient organic transformations

Prodrugs containing lipid moieties attached to drug derivatives, such as anti-cancer drug derivatives, via linkers comprising disulfide groups are described. Also described are nanoparticles coated with a lipid layer containing the prodrugs, formulations comprising the nanoparticles, and the use of the nanoparticles in methods of treating diseases, such as cancer, alone or in combination with additional drug compounds, targeting agents, and/or immunotherapy agents, such as immunosuppression inhibitors that target the CTLA-4, PD-1/PD-L1, IDO, LAG-3, CCR-7 or other pathways, or multiple immunosuppression inhibitors targeting a combination of such pathways. Optionally, the nanoparticles can comprise a photosensitizer or a derivative thereof and can be used in methods involving photodynamic therapy. Synergistic therapeutic effects result from combinations of multiple modalities provided by the disclosed nanoparticles and/or nanoparticle formulations.

Nanoparticles for chemotherapy, targeted therapy, photodynamic therapy, immunotherapy, and any combination thereof

Metal-organic framework (MOFs) compositions based on post&#xac;synthetic metalation of secondary building unit (SBU) terminal or bridging OH or OHgroups with metal precursors or other post-synthetic manipulations are described. The MOFs provide a versatile family of recyclable and reusable single-site solid catalysts for catalyzing a variety of asymmetric organic transformations, including the regioselective boryiation and siiylation of benzyiic C&#x2014;H bonds, the hydrogenation of aikenes, imines, carbonyls, nitroarenes, and heterocycles, hydroboration, hydrophosphination, and cyclization reactions. The solid catalysts can also be integrated into a flow reactor or a supercritical fluid reactor.

Stabilization of active metal catalysts at metal-organic framework nodes for highly efficient organic transformations

Metal-organic frameworks (MOFs) comprising photosensitizers are described. The MOFs can also include moieties capable of absorbing X-rays or other ionizing irradiation energy and/or scintillation. Optionally, the photosensitizer or a derivative thereof can form a bridging ligand of the MOF. Further optionally, the MOF can comprise inorganic nanoparticles in the cavities or channels of the MOF or can be used in combination with an inorganic nanoparticle. Also described are methods of using MOFs and/or inorganic nanoparticles in photodynamic therapy, X-ray induced photodynamic therapy, radiotherapy, radiodynamic therapy, or in radiotherapy-radiodynamic therapy, either with or without the co-administration of one or more immunotherapeutic agent and/or one or more chemotherapeutic agent.

Nanoparticles for photodynamic therapy, X-ray induced photodynamic therapy, radiotherapy, radiodynamic therapy, chemotherapy, immunotherapy, and any combination thereof

Metal-organic frameworks (MOFs) comprising photosensitizers are described. The MOFs can also include moieties capable of absorbing X-rays and/or scintillation. Optionally, the photosensitizer or a derivative thereof can form a bridging ligand of the MOF. Further optionally, the MOF can comprise inorganic nanoparticles in the cavities or channels of the MOF or can be used in combination with an inorganic nanoparticle. Also described are methods of using MOFs and/or inorganic nanoparticles in photodynamic therapy or in X-ray induced photodynamic therapy, either with or without the co-administration of one or more immunotherapeutic agent and/or one or more chemotherapeutic agent.

Nanoparticles for photodynamic therapy, X-ray induced photodynamic therapy, radiotherapy, chemotherapy, immunotherapy, and any combination thereof

Metal-organic framework (MOFs) compositions based on nitrogen donor-based organic bridging ligands, including ligands based on 1,3-diketimine (NacNac), bipyridines and salicylaldimine, were synthesized and then post-synthetically metalated with metal precursors, such as complexes of first row transition metals. Metal complexes of the organic bridging ligands could also be directly incorporated into the MOFs. The MOFs provide a versatile family of recyclable and reusable single-site solid catalysts for catalyzing a variety of asymmetric organic transformations. The solid catalysts can also be integrated into a flow reactor or a supercritical fluid reactor.

Metal-organic frameworks containing nitrogen-donor ligands for efficient catalytic organic transformations

Nanoscale coordination polymer nanoparticles for the co-delivery of multiple therapeutic agents are described. The multiple therapeutic agents can include a combination of different chemotherapeutic agents, a combination of one or more chemotherapeutic agents and one or more nucleic acids, such as small interfering RNA (siRNA) or microRNA, a combination of one or more chemotherapeutic agents and a photosensitizer (i.e., for use in photodynamic therapy), or a plurality of different siRNAs. Pharmaceutical formulations including the nanoparticles, methods of using the nanoparticles to treat cancer, and methods of making the nanoparticles are also described.

Nanoscale carriers for the delivery or co-delivery of chemotherapeutics, nucleic acids and photosensitizers

Metal-organic frameworks (MOFs) comprising photosensitizers are described. The MOFs can also include moieties capable of absorbing X-rays and/or scintillation. Optionally, the photo sensitizer or a derivative thereof can form a bridging ligand of the MOF. Further optionally, the MOF can comprise inorganic nanoparticles in the cavities or channels of the MOF or can be used in combination with an inorganic nanoparticle. Also described are methods of using MOFs and/or inorganic nanoparticles in photodynamic therapy or in X-ray induced photodynamic therapy, either with or without the co-administration of one or more immunotherapeutic agent and/or one or more chemotherapeutic agent.

Metal-organic framework (MOFs) compositions based on chiral phosphine-, chiral oxazoline-, chiral pyridine-, and chiral diene-derived organic bridging ligands were synthesized and then post-synthetically metalated with metal precursors such as Ru and Rh complexes. The metal complexes could also be directly incorporated into the MOFs. The MOFs provide a versatile family of recyclable and reusable single-site solid catalysts for catalyzing a variety of asymmetric organic transformations, including the addition of arylboronic acids to &#x3b1;,&#x3b2;-unsaturated ketones and alkimines, the hydrogenation of substituted alkene and carbonyl compounds, and cyclization reactions. The solid catalysts can also be integrated into a flow reactor or a supercritical fluid reactor.

Growing community of inventors

Chicago, IL, United States of America

Wenbin Lin