Mn-based degradable MOF nano-reactor as well as preparation method and application thereof

A nanoreactor and MOF technology, applied in the field of biomedicine, can solve problems such as large differences in physical and chemical properties and mechanism of action, and achieve the effect of overcoming tumor penetration and cell uptake barriers, overcoming blood circulation barriers, and inhibiting tumor metastasis and recurrence

Pending Publication Date: 2022-04-22
NORTHWESTERN POLYTECHNICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the physical and chemical properties and mechanism of action of GOx and 1-MT are quite different. It is necessary to safely and efficiently overcome complex in vivo delivery barriers (such as blood barriers, tumor tissue barriers, cell uptake barriers, etc.) and improve drug bioavailability. In order to responsively

Method used

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  • Mn-based degradable MOF nano-reactor as well as preparation method and application thereof
  • Mn-based degradable MOF nano-reactor as well as preparation method and application thereof
  • Mn-based degradable MOF nano-reactor as well as preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0051] Embodiment 1 reactor and preparation method thereof

[0052] A Mn-based degradable MOF nanoreactor controlled release system PCP-Mn-DTA@GOx@1-MT, which uses Mn-based ROS-responsive degradable MOF nanoparticles Mn-DTA as the core and functionalized grafting on its surface pH-responsive PEG-CDM-PEI shell, co-loaded with GOx and 1-MT, prepared a controlled release system.

[0053] The preparation process of the Mn-based degradable MOF nanoreactor controlled release system PCP-Mn-DTA@GOx@1-MT includes the following steps:

[0054] (1) Preparation of core Mn-based MOF nanoparticles Mn-DTA:

[0055] 11) Synthesis of ROS-responsive organic ligand 5,5-dimethyl-4,6-dithioazelaic acid (DTA):

[0056] Weigh 4.9mmol 3-mercaptopropionic acid (MPA) and dissolve it in 9.82mmol acetone solution, and stir continuously at room temperature for 8h. Then, the above mixed system was placed in an ice bath (ice-water mixture) overnight to make it crystallize. Filter to collect crystals. S...

experiment example 1

[0073] The product that each step of embodiment 1 obtains is through XRD, TEM, BET, 1 H NMR, DLS and Zeta potential analyzer, GPC, FTIR and other modern nano-testing and analysis techniques have systematically studied its morphology, composition and chemical bonds, and the results are as follows:

[0074] The present invention has analyzed the crystal structure of the Mn-DTA that embodiment obtains by X-ray diffraction, and the result is as follows figure 1 As shown in A, the XRD pattern of Mn-DTA presents strong diffraction peaks at 100°, 002°, 101°, 102°, 110°, 103° and 112°, which are consistent with the crystal structure of MnS compound. Among them, Mn-DTA also exhibited relatively sharp diffraction peaks, indicating that Mn-DTA single crystals have good crystallinity. In addition, the CCDC database calculation results show that Mn 2+ In fact, it coordinates with 3 DTA ligands to form a regular hexagonal prism structure (such as figure 1 As shown in Figure B-D), the thr...

experiment example 2

[0081] pH / ROS-responsive size reduction / charge inversion and drug release properties of Mn-based degradable MOF nanoreactor controlled release system.

[0082] The present invention utilizes H 2 o 2 To simulate the tumor microenvironment ROS, the characteristics of pH-responsive size reduction & charge reversal and ROS-responsive drug release of the system were tested. The specific results are as follows:

[0083] 1) PCP-Mn-DTA@GOx@1-MT controlled-release system pH-responsive size reduction & charge-reversal properties

[0084] The pH-responsive size reduction and charge inversion characteristics of the PCP-Mn-DTA@GOx@1-MT controlled release system were investigated by DLS and Zeta. Such as Figure 5As shown in Figure A, the size of PCP-Mn-DTA@GOx@1-MT is 97±4.5nm at pH 7.4 (simulating normal physiological conditions), while at pH 6.8 (simulating low acid stimulation of tumor microenvironment) After 4 hours of incubation at high temperature, the particle size decreased to...

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Abstract

The invention discloses a Mn-based degradable MOF nano-reactor and a preparation method and application thereof, the nano-reactor comprises an inner core Mn-based MOF nano-particle, the surface of the inner core Mn-based MOF nano-particle is functionalized and grafted with a pH responsive shell copolymer PEG-CDM-PEI, and the Mn-based MOF nano-particle is loaded with a biological enzyme GOx and an IDO immunosuppressor. The pH/ROS dual-responsive MOF nanoreactor drug controlled release system co-loaded with an immune checkpoint IDO inhibitor 1-MT and GOx is prepared by utilizing the advantages of high loading capacity, enzyme reaction space limitation, ROS responsive degradability and the like of an MOF nanoreactor, and tumor hunger/oxidation/IDO immune combined therapy is regulated and controlled. The drug-controlled system can respond to a weakly acidic tumor microenvironment, induce size reduction/charge reversal, overcome in-vivo tumor permeation and cell barrier, and improve the delivery efficiency; in addition, the self-enhanced MOF degradation and drug release performance is achieved; moreover, the immune therapy mediated by the drug control system can effectively inhibit the immune tolerance, enhance the anti-tumor immune response of the body and inhibit the growth, metastasis and relapse of tumors.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a Mn-based degradable MOF nanoreactor and its preparation method and application. Background technique [0002] The malignant proliferation of tumors seriously endangers human health, and immunotherapy can restore the body's anti-tumor immune response and kill tumors efficiently, which has potential clinical application prospects. For example, immunotherapy represented by inhibition of immune checkpoints (such as indoleamine 2,3-dioxygenase, IDO) can significantly inhibit the body's immune tolerance and restore the activity of various effector T cells, and the early clinical effect is remarkable. However, insufficient immune response and low bioavailability hinder its clinical application. Another example is that glucose oxidase (GOx)-mediated tumor starvation therapy can not only competitively consume the glucose necessary for its growth, but also generate reactive oxygen s...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/60A61K38/44A61K31/405A61P35/00A61P35/04B82Y5/00B82Y40/00C08G83/00
CPCA61K47/6949A61K47/60A61K47/6935A61K38/443A61K31/405A61P35/00A61P35/04C12Y101/03004B82Y5/00B82Y40/00C08G83/008A61K2300/00
Inventor 戴亮亮姚梦娇付振祥李想孟思雨郑薪民袁璋
Owner NORTHWESTERN POLYTECHNICAL UNIV
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