Core-shell type double-ligand coordination polymer as well as preparation method and application thereof
A technology of coordination polymers and coordination compounds, applied in the field of nanotechnology, to achieve the effects of improving curative effect, avoiding uneven biodistribution, increasing binding strength and drug loading
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Embodiment 1
[0043] In this example, a HA-modified core-shell dual-ligand coordination polymer nanoparticle loaded with liver microsomal enzymes was constructed, which has high water solubility, stability and biocompatibility. The combination of drugs (second ligands) and enzymes enhances the stability and efficacy of the anti-melanoma drug DTIC ( figure 1 ). In this example, through in vitro characterization, stability studies, drug and enzyme release assays, cell uptake and cytotoxicity studies, etc., it is demonstrated that the above coordination polymer nanoparticles are suitable for in vivo anti-tumor therapy. Example 1 Construction of HA-modified liver microsomal enzyme-loaded core-shell dual-ligand coordination polymer nanoparticles
[0044] First, according to the calculation results, the required DTIC was accurately weighed and dissolved in methanol-water (50:50) to obtain a 0.027M DTIC solution, and 3.45M 2-methylimidazole aqueous solution, 1M tris(hydroxymethyl) solution were p...
Embodiment 2
[0057] Example 2 Evaluation of the stability, drug and enzyme release ability and biocompatibility of HA-modified liver microsomal enzyme-loaded core-shell dual-ligand coordination polymer nanoparticles
[0058] stability:
[0059] Take 2 mg of CZDH freshly prepared in Example 1, and divide it into four equal parts and resuspend in 0.03M PBS (pH=7.4), 0.03M PBS (pH=5.5), 0.2M PBS (pH=7.4), 0.03M PBS (pH=7.4), And in DMEM cell culture medium containing 10% heat-inactivated fetal bovine serum, the hydrodynamic diameters were measured at 0, 1, 2, 4, 6, 8, 10, 24, 48, and 72h, respectively.
[0060] DLS-time correlation curve ( Figure 4 ) showed that CZDH maintained good particle size stability in three solutions: 0.03M PBS (pH=7.4), 0.2M PBS (pH=7.4), and DMEM cell culture medium containing 10% heat-inactivated fetal bovine serum. However, CZDH exhibited a significant increase in the hydrodynamic diameter in 0.03M PBS (pH=5.5), which was due to the protonation of the imidazole g...
Embodiment 3
[0068] Example 3 Cell uptake study of HA-modified core-shell dual ligand coordination polymer nanoparticles
[0069] Preparation of HA-modified fluorescein isothiocyanate (FITC)-loaded core-shell dual ligand coordination polymer nanoparticles:
[0070] Example 1 was followed except that 0.1 mg / mL liver microsomal enzyme was replaced by 1.94 μg / mL FITC (5 μM). The FITC-loaded nanoparticles were denoted as ZDH / FITC.
[0071] Cellular Uptake Assay:
[0072] B16F10 cells were seeded in six-well plates at a seeding density of 1 × 10 5 pcs / well, and in 5% CO 2 Incubate overnight in a sterile incubator (37°C, saturated humidity). After 24 hours, the original culture solution was aspirated, and DMEM medium containing 5 μM ZDH / FITC (in terms of FITC concentration) was added, and the incubation was continued in the incubator. After 0, 1, 2, 4, 8, and 12 h, the DMEM medium was discarded, washed three times with PBS solution, and the cells were trypsinized and centrifuged. The tryps...
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