Simulation-responsive targeting polysaccharide supermolecular diagnosis and treatment assembly and preparation method thereof
A stimuli-response and assembly technology, which is applied in the field of targeted polysaccharide supramolecular diagnosis and treatment assembly and its preparation, can solve the problems of poor water solubility and stability of the carrier, complex synthesis and separation process, etc., and achieve simple construction method and good application foreground effect
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Embodiment 1
[0033] A stimuli-responsive targeted polysaccharide supramolecular therapeutic assembly, the building blocks of which are cyclodextrin-modified hyaluronic acid and disulfide-linked adamantane naphthalimide camptothecin prodrug, through cyclodextrin and adamantine The host-guest interaction between alkanes forms an assembly with hydrophilic hyaluronic acid as the shell and hydrophobic camptothecin as the core. The shape of the assembly is spherical nanoparticles with a particle size of 260-280nm. Thiol-type reducing agents have good drug release responsiveness. Wherein the cyclodextrin modified hyaluronic acid molecular formula is (C 14 h 21 NO 11 ) 1175 (C 58 h 95 N 3 o 44 ) 196 , an average of 7 hyaluronic acid units are modified with a cyclodextrin unit, and the molecular formula of the disulfide-linked adamantine naphthalimide camptothecin prodrug is C 44 h 52 Cl 2 N 4 o 7 S 2 , the structure of the assembly building unit is as follows:
[0034]
[0035] T...
Embodiment 2
[0049] Experimental verification of the stimulus responsiveness of the assembly:
[0050] Dithiothreitol (DTT) was chosen as the model reducing agent. For the measurement of ultraviolet spectrum and fluorescence spectrum, the mother solution of the assembly prepared above was diluted to 5 μM with pH 7.4 and phosphate buffer solution with a concentration of 0.01M, and 3 mL of the solution was added to 7 mL centrifuge tubes, one of which was added 5 mM DTT, After incubating the two centrifuge tubes in a water bath at 37°C for 2 h, they were detected by an ultraviolet spectrometer ( Figure 4 ) and fluorescence spectrometer detection ( Figure 5 ). from Figure 4 It can be seen that after incubation with DTT, a new absorption peak appears at 400-500nm, from the fluorescence spectrum Figure 5 It can be seen that after incubation with DTT, the emission wavelength is red-shifted and the emission intensity increases. These results indicate that the polysaccharide supramolecular ...
Embodiment 3
[0052] Application of the assembly in the field of cancer therapy
[0053] Concrete application effect of the present invention is as follows:
[0054]Spread HCT-116 cells (human colon cancer cells) and NIH3T3 (mouse embryonic fibroblasts) in 96-well plates containing 10% fetal bovine serum in DMEM medium for 24 hours, and add cyclodextrin to modify hyaluronic acid Acid (HACD), camptothecin (CPT), assembly (HACD-AdaCPT), assembly containing excess hyaluronic acid (HACD-AdaCPT+HA), cultured continuously for 48 hours, measured by MTT method under each experimental condition cell viability.
[0055] Image 6 It is the result of cytotoxicity of HCT-116 cells. The figure shows that: within 48h, the HACD-AdaCPT assembly exhibited a similar inhibitory effect on HCT-116 tumor cells as CPT. When excessive hyaluronic acid was added, the cell surface After the hyaluronic acid receptors were saturated, the inhibitory effect of the assembly on HCT-116 cells was weakened, indicating that...
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