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Bispecific PSMA/GRPr targeted bimodal imaging nano contrast agent as well as preparation method and application thereof

A nano-contrast agent, bispecific technology, applied in the field of biomedicine, can solve problems such as poor effect of prostate cancer, and achieve the effect of enhancing active targeting effect, increasing hydrophilicity, and enhancing photothermal effect

Active Publication Date: 2020-08-21
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] Aiming at the above-mentioned technical problems in the prior art, the present invention provides a bispecific PSMA / GRPr targeted dual-modal imaging nano-contrast agent and its preparation method and application. The bispecific PSMA / GRPr Targeted dual-modal imaging nano-contrast agent and its preparation method and application to solve the technical problem that the existing technology is not effective in diagnosing prostate cancer

Method used

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  • Bispecific PSMA/GRPr targeted bimodal imaging nano contrast agent as well as preparation method and application thereof
  • Bispecific PSMA/GRPr targeted bimodal imaging nano contrast agent as well as preparation method and application thereof
  • Bispecific PSMA/GRPr targeted bimodal imaging nano contrast agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1: Preparation of bispecific PSMA / GRPr targeted dual-modality imaging nanocontrast agent

[0047] A method for preparing a dual-mode imaging nano-contrast agent, the steps are as follows:

[0048] ① Accurately weigh 15mg PLGA-mPEG copolymer, 5mg PLGA-PEG-MAL copolymer, 4mg oleic acid modified Fe 3 o 4 Nanoparticles and pipette 40 uL of 1H-perfluoropentane dissolved in 1 mL of dichloromethane;

[0049] ② Add the above solution dropwise to the polyvinyl alcohol solution with a concentration of 4% by mass;

[0050] ③Use an ultrasonic cell pulverizer to emulsify the above mixture into balls under ice-water bath conditions;

[0051] ④Magnetically stir the mixture to fully volatilize the dichloromethane;

[0052] ⑤ The nanoparticles were centrifuged and washed 3 times, resuspended in ultrapure water and stored at 4°C. ,

[0053] ⑥ Disperse the nanoparticles obtained in the previous step into the PBS solution of PH=7.2, the material ratio of the nanoparticles to ...

Embodiment 2

[0062] Example 2: Safety assessment of bispecific PSMA / GRPr targeted dual-modality imaging nanocontrast agent

[0063] like Image 6 As shown, after incubating GBP-PS nanoparticles with prostate cancer C4-2 and PC3 cells for 24 hours, the cell viability remained above 90% even with an iron concentration as high as 200 μg / mL, which indicated the cytotoxicity of GBP-PS nanoparticles Low.

[0064] Get GBP-PS nanoemulsion 200ul to inject in the mouse body from tail vein (iron dosage 16mg kg -1 ), the tail vein of mice in the control group was injected with 200ul normal saline, and after 14 days of observation, blood was taken for whole blood analysis and blood biochemical detection, and HE staining was performed on the heart, liver, spleen, lung, and kidney. The results showed that each of the experimental group and the control group There was no significant difference in the blood test indexes and slices of various organs, indicating that GBP-PS nanoparticles have high safety i...

Embodiment 3

[0065] Example 3: Evaluation of cell targeting of bispecific PSMA / GRPr targeted dual modality imaging nanocontrast agents

[0066] After incubating GBP-PS nanoparticles with prostate cancer C4-2 (high expression of PSMA and low expression of GRPr) and PC3 (high expression of GRPr and low expression of PSMA) cells for 6 hours, confocal laser microscopy images showed that C4-2 ( Figure 7 a) and PC3 ( Figure 7 b) A large amount of FITC green fluorescence of GBP-PS is seen in the cytoplasm of the cells, indicating that the two types of cells have taken up a large amount of GBP-PS nanoparticles, and the PSMA antagonist 2-PMPA or the GRPr-binding peptide Bombesin can obviously competitively inhibit the corresponding Cells uptake it, while C4-2 and PC3 cells have only a small amount of uptake of nanoparticles without targeting peptide (FP-PS). The results demonstrated the specific targeting of GBP-PS nanoparticles to C4-2 and PC3 cells.

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Abstract

The invention belongs to the field of contrast agents, and provides a bispecific PSMA / GRPr targeting bimodal imaging nano contrast agent, PLGA-PEG is used as a shell membrane, liquid fluorocarbon 1H-perfluoropentane and Fe3O4 nanoparticles are wrapped in the PLGA-PEG, and a heterodimer polypeptide is connected to the shell of the PLGA-PEG. The invention also provides an application of the contrastagent in preparing a medicine for diagnosing or treating prostatic cancer. The invention also provides a preparation method of the contrast agent. The average particle size of the prepared nano contrast agent is 213.7 + / -65.27 nm; Fe3O4 nanoparticles play a role in magnetic resonance imaging, 1H-perfluoropentane has the characteristics of liquid-gas phase change and has the advantages of stability and low energy required by phase change, the effects of ultrasonic and photoacoustic imaging, drug controlled release and the like are played, and the designed polypeptide can efficiently and specifically target prostate cancer cells. The nano contrast agent provided by the invention can simultaneously target two important target points PSMA and GRPr of prostate cancer.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a contrast agent, in particular to a bispecific PSMA / GRPr targeted dual-mode imaging nano-contrast agent and its preparation method and application. Background technique [0002] Prostate cancer lesions are sporadic, multifocal, and difficult to be accurately detected by imaging techniques. At present, the value of imaging techniques in the diagnosis and staging of prostate cancer is still unsatisfactory, and its sensitivity and specificity still cannot rule out random puncture. Finding an imaging method that can accurately detect prostate cancer is a clinical problem that needs to be solved urgently. The rapid development of nanomedicine provides a new means to solve the above problems. The construction of targeted molecular probes can pass through the microvessels of prostate tumors, enter the interstitial space, specifically bind to prostate cancer cells, and have a good enhanced imag...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22A61K49/18A61K49/14
CPCA61K49/225A61K49/1866A61K49/14A61K49/0002
Inventor 谢少伟薛蔚董柏君李凤华
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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