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Application of nanoscale coordination polymer Hemin (at) Gd-NCPs

A coordination polymer, nano-scale technology, applied in the field of biomedicine, can solve the problems of radiation therapy failure and weakening ability, and achieve the effect of activating the body's anti-tumor immune response, promoting release, and inhibiting liver and lung metastasis.

Inactive Publication Date: 2021-06-25
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This causes the hydroxyl radicals produced by RT to be consumed by GSH, which further weakens the ability of RT to generate ROS, eventually leading to the failure of radiotherapy

Method used

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  • Application of nanoscale coordination polymer Hemin (at) Gd-NCPs
  • Application of nanoscale coordination polymer Hemin (at) Gd-NCPs
  • Application of nanoscale coordination polymer Hemin (at) Gd-NCPs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 Hemin@Gd-NCPs-mediated radiation therapy induces strong eversion of CRT in tumor cells

[0035] First, CT26 cells were seeded on a 24-well plate at a density of 100,000 cells per well and cultured for 12 hours. Then, the Gd-NCPs ([Gd 3+ ]=100μM) and H@Gd-NCPs ([Gd 3+]=100 μM, [Hemin]=10 μM) were added to the cells respectively, and then transferred to an anaerobic chamber to continue treatment for 12 hours. After CT26 cells were irradiated (8Gy×1), they were cultured for 4 hours and washed 3 times with PBS. Tumor cells were incubated with Alexa Fluor 488-CRT antibody (dilution 1:500, Abcam, UK) for 1 hour and stained with DAPI. Immunofluorescence images were from Nikon Eclipse Ti (Japan) and analyzed using ImageJ software.

[0036] The result is as Figure 1a As shown, Hemin@Gd-NCPs-mediated radiotherapy treatment significantly induced CRT eversion in tumor cells, exhibiting the strongest green fluorescence signal.

Embodiment 2

[0037] Example 2 Hemin@Gd-NCPs mediated radiation therapy significantly induced tumor cells to secrete HMGB1 and ATP.

[0038] Detection of HMGB1 and ATP release. The concentration of HMGB1 in the cytoplasm and cell supernatant after each treatment was determined by using an ELISA kit (Ying Feixue Biotechnology, China) according to the instructions. ATP kit (Beyotime, China) was used to measure the concentration of ATP in the cell supernatant of each group according to the detection steps of the kit. Using a microplate reader ( Nivo) to detect fluorescence and absorbance.

[0039] The result is as Figure 1b , as shown in c. The concentration of HMGB1 and ATP in the Hemin@Gd-NCPs plus radiotherapy group measured by the kit was significantly higher than that in other groups.

Embodiment 3

[0040] Example 3 Hemin@Gd-NCPs-mediated radiation therapy significantly promoted the activation of DC cells in the draining lymph nodes of CT26 tumor-bearing mice.

[0041] In order to evaluate the maturation of DCs, CT26 tumor-bearing mice (110-130mm 3 ) were divided into 6 groups, which were given normal saline, [Gd 3+ ]=30mg / kg Gd-NCPs group, [Gd 3+ ]=30mg / kg and [Hemin]=12.5mg / kg H@Gd-NCPs group (6Gy×1) and normal saline, Gd-NCPs group, H@Gd-NCPs without radiotherapy group. Mice were sacrificed 5 days after radiation, and tumor-draining lymph nodes (TDLN) were collected for flow cytometry analysis. TDLNs were ground into a single cell suspension, mixed with FITC anti-mouse CD11c (0.25 μg per million 100 μL cell volume), PE anti-mouse CD86 (0.25 μg per million 100 μL cell volume), APC anti-mouse CD80 (1.0 μg 100 μL cell volume per million) were co-incubated with antibodies (BioLegend, USA), and then detected by flow cytometry.

[0042] The result is as figure 2 shown....

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Abstract

The invention provides an application of a nanoscale coordination polymer Hemin (at) Gd-NCPs, the Hemin (at) Gd-NCPs is used for enhancing radiotherapy, and oxidative stress induced by radiotherapy can be amplified through two aspects of X-ray deposition and GSH elimination. Radiotherapy-induced tumor cell immunogenicity death is enhanced by amplifying radiotherapy-induced oxidative stress, release of DAMPs is promoted, and DC cell activation is effectively promoted; the anti-tumor immune response of an organism is effectively activated by utilizing the radiotherapy sensitization effect mediated by the Hemin-coated Gd-NCPs, the intratumor infiltration of CD4 < + > / CD8 < + > T cells is promoted, the intratumor IFN-gamma content is increased, the tumor immunosuppression microenvironment is improved, and the synergistic effect of radiotherapy and an immune checkpoint inhibitor is enhanced when the Hemin-coated Gd-NCPs is combined with an inhibitor alphaPD-L1; the combination of radiotherapy and alphaCTLA-4 can effectively inhibit liver and lung metastasis of 4T1 tumors and prolong the lifetime of tumor-bearing mice.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to the application of supramolecular chemical self-assembled nanoscale coordination polymer Hemin@Gd-NCPs, in particular to the application of Hemin@Gd-NCPs for enhancing combined therapy of radiotherapy and immune checkpoint inhibitors . Background technique [0002] Radiation therapy (RT) has always been the mainstream method of clinical cancer treatment, which uses exogenous high-energy ionizing radiation (such as X-rays) to generate free radicals to damage the DNA of tumor cells. Due to its low systemic side effects and broad-spectrum efficacy, more than 50% of clinical cancer patients currently include radiotherapy in their treatment regimens. [0003] A large number of in vitro studies have confirmed that radiotherapy can achieve immune regulation by inducing immunogenic death. Specifically, in addition to directly causing tumor cell death, X-rays are accompanied by the release of t...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K39/395A61K31/555A61P35/00A61P35/04A61K49/10
CPCA61K41/0057A61K39/39558A61K31/555A61P35/00A61P35/04A61K49/101A61K2039/844A61K2039/86A61K2300/00
Inventor 胡一桥吴锦慧袁阿虎汪钰翔
Owner NANJING UNIV
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