Preparation method and application of amphiphilic prodrug and nanoparticle thereof for active targeted therapy of tumors
An active targeting, nanoparticle technology, applied in the preparation methods of peptides, anti-tumor drugs, pharmaceutical formulations, etc., can solve the problems of normal tissue or organ toxicity, weak targeting, poor selectivity, etc., and achieve good tumor targeting. Ability, Reduced Toxicity, Selective Effects
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0032]
[0033] 1.1 Synthesis of Intermediate A-1
[0034] 3,3'-propane-2,2-diylbis(sulfadiyl)dipropionic acid (TK, 252.05mg), 1-ethyl-(3-dimethylaminopropyl)carbodiimide Add hydrochloride (EDCI, 287.55mg), 4-dimethylaminopyridine (DMAP, 12.2mg) and anhydrous triethylamine (TEA, 0.28mL) into the reaction flask, then add 25mL of anhydrous dichloromethane, and stir at room temperature After reacting for 1 hour, Epothilone B (507.27 mg) was added, followed by stirring and reacting at room temperature for 24 hours. After the reaction finishes, add 20mL deionized water for extraction, collect the organic phase, use dichloromethane and methanol volume ratio as (20:1) mixed solution as eluent, obtain white powdery intermediate A through column chromatography 1 (345.92 mg, 46.6% yield), MS m / z (ESI): 742.3039 [M+H] + . 1 H NMR (CDCl 3 ,400MHz)δ7.04(1H,s),6.82(1H,bs),5.34(1H,dd),5.26(1H,dd),4.21(1H,m),4.19(1H,bs),3.56(1H ,dq),2.93(4H,m),2.84(1H,dd),2.75(3H,s),2.69(4H,m),2.51(1H...
Embodiment 2
[0044] This example provides an experiment on the effect of amphiphilic prodrug nanoparticles used for active tumor targeting therapy on cancer cells.
[0045] The amphiphilic prodrug nanoparticles (Assembly of A) prepared in Example 1 and the bulk drug Epothilone B (Epothilone B) were formulated with cell culture medium to concentrations of 1.25, 2.5, 5, 10, 15 , 20, 40, and 80nmol / L solutions, and then respectively cultured with HCT116 cells (colon cancer cells) and PC-3 cells (prostate cancer cells) for 48 hours, using the MTT method for cell activity testing, the results are as follows Figure 4 shown. Epothilone B exhibited an efficient effect of killing cancer cells at a concentration of 2nmol / L; at the same time, when the concentration of amphiphilic prodrug nanoparticles reached 15nmol / L, it also showed a very good effect. The ability to kill cancer cells, and the killing effect of amphiphilic prodrug nanoparticles on cancer cells is proportional to the concentration....
Embodiment 3
[0047] Fluorescent imaging experiments of the amphiphilic prodrug nanoparticles used for active tumor targeting therapy in vivo in tumor-bearing nude mice.
[0048] Using Cy5.5 as the fluorescent probe molecule in vivo, Cy5.5 was encapsulated in the amphiphilic prodrug nanoparticles obtained in Example 1, and the targeting effect of the nanoparticles was evaluated. Digest PC-3 cells in the logarithmic growth phase, count, and prepare 4.0×10 6 cells / mL cell suspension, inoculated subcutaneously into the right anterior axillary of nude mice, each inoculated 200 μL, when the tumor grew to a volume of about 500mm 3 2 mice were randomly selected. 200 μL of Cy5.5-loaded nanoparticles were injected into PC-3 tumor-bearing mice through the tail vein. After 12 hours of injection, the ZKKS-Mulaurora imaging system was used to take pictures and analyze the fluorescence intensity of the whole body of the mice. The result is as Figure 5 shown. After the amphiphilic prodrug nanopartic...
PUM
| Property | Measurement | Unit |
|---|---|---|
| particle diameter | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More