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Metal-organic frameworks, and pharmaceutic preparation and application thereof

A technology of use and inhibitor, applied in the fields of metal-organic frameworks, pharmaceutical preparations and their use in the preparation of medicines, can solve problems such as limiting the efficacy of PDT

Pending Publication Date: 2020-01-31
UNIVERSITY OF CHICAGO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, despite the photochemical properties of these molecules to efficiently generate ROS, suboptimal tumor accumulation of these molecules after systemic administration limits the efficacy of PDT in the clinic

Method used

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  • Metal-organic frameworks, and pharmaceutic preparation and application thereof
  • Metal-organic frameworks, and pharmaceutic preparation and application thereof
  • Metal-organic frameworks, and pharmaceutic preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0204] According to an exemplary embodiment of the presently disclosed subject matter (further described in the Examples below), Hf-porphyrin NMOFs were prepared and used as PS for PDT against drug-resistant head and neck cancer. Without wishing to be bound by any theory, it is believed that the porphyrin-derived bridging ligands were incorporated into stable and porous UiO (Universitetet I Oslo (named after the Norwegian for University of Oslo). Has suitable morphology and size The NMOF structure can provide multiple advantages over other nanoparticle PDT reagents. First, PS molecules or parts can be sufficiently separated in the NMOF framework to avoid aggregation and self-quenching of excited states. Second, Formation of coordination bonds between porphyrin ligands and heavy metal (e.g., Hf) centers can facilitate the transition between systems to increase the efficiency of ROS generation. Third, the porous NMOF structure can provide a pathway for ROS (e.g., singlet oxygen (...

Embodiment 1

[0296] DBP-Hf-like NMOFs for PDT

[0297] 1.1. Materials and cell lines

[0298] Unless otherwise stated, all starting materials were purchased from Sigma-Aldrich (St. Louis, Missouri, United States of America) and Thermo Fisher Scientific (Waltham, Massachusetts, United States of America). States of America)) and used without further purification.

[0299] The human head and neck cancer cell line SQ20B (cisplatin-resistant) was kindly provided by Dr. Stephen J. Kron (Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, USA). In DMEM / F12 (1:1) medium (Gibco, Grand Island, New York, USA) containing 20% ​​fetal bovine serum (FBS, Hyclone, Logan, Utah, USA) Culture cells in.

[0300] Athymic female nude mice (6 weeks, 20-22 g) were provided by Harlan Laboratories, Inc (Dublin, Virginia, USA). The study protocol was reviewed and approved by the University of Chicago Animal Care and Use Committee (IACUC).

[0301] 1.2.5,15-bis(p-benzoyloxy)porphyr...

Embodiment 2

[0349] Overview of the characterization of DBP MOFs

[0350] The porphyrin derivative 5,15-bis(p-benzoyloxy)porphyrin (H 2 DBP), and end with 1 H and 13 C NMR and mass spectral characterization. The linearly arranged dicarboxylate groups of the DBP ligand can be constructed with the framework formula Hf 6 (μ 3 -O) 4 (μ 3 -OH) 4 (DBP) 6 The DBP-UiONMOF. by HfCl 4 and H 2 DBP-UiO was synthesized by solvothermal reaction of DBP in N,N-dimethylformamide (DMF) at 80℃. The resulting dark purple powder was washed sequentially with copious amounts of DMF, 1% triethylamine in ethanol (v / v) and ethanol, and then dispersed in ethanol to form a stock suspension.

[0351] Analogue Zr based on DBP-UiO 6 (μ 3 -O) 4 (μ 3 -OH) 4 (Zn-DPDBP) 6 (i.e., Zn-DPDBP-UiO, where DPDBP is 5,15-(p-benzoyloxy)-10,20-diphenylporphyrin), and DPDBP and DBP have similar lengths, and The powder X-ray diffraction (PXRD) pattern of Zn-DPDBP-UiO is similar to that of DBP-UiO. It is believed that ...

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Abstract

The present invention provides metal-organic frameworks, and pharmaceutic preparation and application thereof. The 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.

Description

[0001] This application is a divisional application of Chinese Patent Application No. 201580068173.X entitled "A metal-organic framework, a pharmaceutical preparation and its use in the preparation of medicine" with an application date of October 14, 2015. [0002] Citations to related applications [0003] The presently disclosed subject matter claims U.S. Provisional Patent Application Serial No. 62 / 063,770, filed October 14, 2014; and U.S. Provisional Patent Application Serial No. 62 / 173,103, filed June 9, 2015. Interest, the disclosure of each case is hereby incorporated by reference in its entirety. [0004] government interest [0005] This invention was made with government support under Grant Numbers U01-CA151455, U01-CA198989, and 1S10RR026988-01 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0006] The presently disclosed subject matter provides a nanocarrier platform based on metal-organic fram...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/395A61K31/409A61K31/5415A61K31/28A61K31/282B82B1/00B82Y5/00A61K9/00A61K41/00A61P35/00A61P35/04
CPCA61K31/282A61K31/409B82Y5/00A61K41/0038A61K41/0057A61K41/0071A61K31/337A61K31/405A61K31/4188A61K31/4745A61K31/519A61K31/704A61K9/0009A61P35/00A61P35/02A61P35/04A61K31/395
Inventor 林文斌何春柏卢旷达
Owner UNIVERSITY OF CHICAGO
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