Immunologic adjuvant functionalized metal organic framework material as well as preparation method and application thereof

A metal organic framework and immune adjuvant technology, applied in the preparation and application of immune adjuvant functionalized materials, can solve the problems of long degradation cycle of carrier materials, low photosensitive drug loading efficiency, and high early release rate, and achieve excellent singlet state. Oxygen generation ability, excellent photothermal conversion ability, the effect of improving the therapeutic effect

Active Publication Date: 2020-12-01
DERMATOLOGY HOSPITAL SOUTHERN MEDICAL UNIV (GUANGDONG PROVINCIAL DERMATOLOGY HOSPITAL GUANGDONG PROVINCIAL CENT FOR STI & SKIN DISEASES CONTROL & PREVENTION RES CENT FOR LEPROSY CONTROL & PREVENTION CHINA)
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, a variety of nanocarrier systems have greatly improved the bioavailability and tumor enrichment rate of photosensitive molecules, but there are still many problems such as potential toxicity, low photosensitive drug loading efficiency and high early release rate, etc.
This is attributed to the long degradation cycle of the introduced carrier material or even non-degradable, the loading of photosensitive drugs is limited to non-covalent interactions, and no covalent interaction force is introduced, which greatly reduces the stability of the carrier system.

Method used

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  • Immunologic adjuvant functionalized metal organic framework material as well as preparation method and application thereof
  • Immunologic adjuvant functionalized metal organic framework material as well as preparation method and application thereof
  • Immunologic adjuvant functionalized metal organic framework material as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1 ICG-CpG@MOF material synthesis

[0051] Synthesis of ICG-CpG@MOF materials mainly includes three parts: Synthesis of MIL-101-NH 2 (MOF), ICG and MOF combine to form MOF-ICG, and MOF-ICG loads CpG.

[0052] MIL-101-NH 2 (MOF) synthesis process is as follows:

[0053] (1) 375mg 2-aminoterephthalic acid and 1125mg FeCl 3 ·6H 2 O was dissolved in 12.5ml dimethylformamide respectively;

[0054] (2) Put the two liquids in (1) into a 50ml stainless steel autoclave, and process the mixture at 120°C for 24 hours;

[0055] (3) Centrifuge the liquid obtained in (2) at 8000rpm for 10 minutes, discard the supernatant, collect the precipitate, and obtain the precipitated powder;

[0056] (4) Wash the precipitated powder in (3) three times successively with dimethylformamide and ethanol;

[0057] (5) Dry the washed powder of (4) in vacuum at 50°C for 8 hours, and at this time, MIL-101-NH 2 (MOF).

[0058] Combination of ICG and MOF:

[0059] (6) EDC (100 mM, 10 μL)...

Embodiment 2

[0066] Example 2 Photodynamic and photothermal effects of ICG-CpG@MOF materials

[0067] (1) Dissolve the ICG-CpG@MOF material in deionized water so that the concentration of the ICG-CpG@MOF material in the system is 100 μg / mL; place the solution at 0.5, 1.0, 1.5, 2W / cm 2 Irradiated by a near-infrared laser with a wavelength of 808nm for 0-5 minutes, and recorded the temperature change; Figure 5 As shown, the temperature of the material gradually increased within 5 minutes, and the temperature reached a stable level after 5 minutes and remained at a high level, which proves that the material has a good light-to-heat conversion ability. In addition, if Figure 5 As shown in C, ICG-CpG@MOF can well repeat the photothermal conversion induced by 808nm laser (1.5W / cm2). The following experiments were irradiated with 808nm laser (1.5W / cm2) for 5min.

[0068] (2) In order to test the photodynamic effect of the material, ICG-CpG@MOF material (final concentration 20nM, the same fin...

Embodiment 3

[0069] Example 3 The killing effect of ICG-CpG@MOF material on 4T1 tumor cells

[0070] The 4T1 cells in the logarithmic growth phase were inoculated into 6-well culture plates and cultured overnight. After the cells were completely attached to the wall, the old medium was discarded and divided into: control group, simple ICG-CpG@MOF group, simple laser group, ICG -CpG@MOF+laser group, after corresponding grouping treatment, use a commercially available apoptosis detection kit to process, and flow cytometry to detect apoptosis. The result is as Figure 5 As shown in F, it can be seen from the figure that the tumor cells in the ICG-CpG@MOF group and the laser group alone had no significant changes compared with the control group, and the apoptosis rate in the ICG-CpG@MOF+laser group was significantly increased, which proved that during the phototherapy process The material has a good effect of promoting tumor cell apoptosis.

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Abstract

The invention discloses an immunologic adjuvant functionalized metal organic framework material as well as a preparation method and application thereof. The preparation process comprises the followingsteps: synthesizing MIL-101-NH2, namely MOF, combining ICG with MOF to form MOF-ICG, and loading CpG on MOF-ICG. The material can be applied to preparation of medicines. The material has the advantages that (1) the ultraviolet-visible absorption spectrum peak value of the material provided by the invention is about near-infrared light; the near-infrared laser with single wavelength can be used for exciting photodynamic and photothermal effects at the same time, has excellent singlet oxygen generation capability and photothermal conversion capability under the irradiation of the near-infraredlaser, and has huge application potential in the aspect of tumor phototherapy; (2) in a tumor microenvironment, the material-loaded CpG and TAA released by photodynamic and photothermal therapy jointly activate an immune system, so that the tumor cytotoxicity is enhanced, and the treatment effect is improved; and (3) the material provided by the invention has a tumor multi-modal imaging (fluorescence, photoacoustic, photo-thermal and nuclear magnetic resonance) function, and can be used for monitoring the tumor position and the treatment effect.

Description

technical field [0001] The invention relates to the technical field of a photodynamic and photothermal therapy carrier, in particular to the preparation and application of an immune adjuvant functionalized material. Background technique [0002] Photodynamic and photothermal therapy, as a promising therapeutic method, has received more and more attention in the field of tumor treatment. In recent years, a variety of nanocarrier systems have greatly improved the bioavailability and tumor enrichment rate of photosensitive molecules, but there are still many problems such as potential toxicity, low photosensitive drug loading efficiency and high early release rate. This is attributed to the fact that the introduced carrier material has a long degradation cycle or even cannot be degraded, and the loading of photosensitive drugs is limited to non-covalent interactions, and no covalent interaction force is introduced, which greatly reduces the stability of the carrier system. Usi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/54A61K39/385A61K41/00A61K49/22A61K49/10A61K49/00A61P35/00
CPCA61K47/542A61K39/385A61K41/0052A61K41/0057A61K49/221A61K49/10A61K49/0052A61K49/00A61P35/00A61K2300/00Y02A50/30
Inventor 廖玉辉樊志金李志嘉吴云霞郑兰
Owner DERMATOLOGY HOSPITAL SOUTHERN MEDICAL UNIV (GUANGDONG PROVINCIAL DERMATOLOGY HOSPITAL GUANGDONG PROVINCIAL CENT FOR STI & SKIN DISEASES CONTROL & PREVENTION RES CENT FOR LEPROSY CONTROL & PREVENTION CHINA)
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