Gel factor precursor loaded with autophagy inhibitor and chemotherapeutic drug, gel material, preparation method and application
An autophagy inhibitor and gel factor technology, applied in the field of supramolecular hydrogel nanomaterials, to achieve the effects of enhancing therapeutic effects, reducing toxic side effects, and improving water solubility and stability
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Embodiment 1
[0048] Pure compound P 1 , P 2 , P 3 and P 4 Synthesis
[0049] The first pure compound P in this example 1 (CPT-COOH), the second pure compound P 2 (HCQ), the third pure compound P 3 (HCQ-COOH) and the fourth pure compound P 4 The synthetic route of (HCQ-COOH-NHS) is as follows:
[0050] Dissolve 2.55 mmol of camptothecin in 25 ml of pyridine, add 10 ml of pyridine solution containing 7.65 mmol of succinic anhydride and 0.255 mmol of dimethylaminopyridine, and react overnight with magnetic stirring at room temperature under the protection of argon. After removal, 10 milliliters of deionized water was added to the residue, and after purification by freeze-drying and high-performance liquid chromatography, camptothecin succinic acid (named as P 1 ).
[0051] 2.3 millimoles of hydroxychloroquine sulfate was dissolved in 10 milliliters of deionized water, 200 microliters of ammonia were added to the solution, stirred at room temperature for 30 minutes, and extracted with...
Embodiment 2
[0055] Pure compound P 5 and P 6 Synthesis
[0056] After 1 mmol of 2-chlorotrityl chloride resin was swelled in 5 ml of N,N-dimethylformamide for 30 minutes, 2 mmol of N-fluorenylmethoxycarbonyl-O-phosphate-L-phenol was added Amino acid, then add 5 mmol N,N-diisopropylethylamine, react for 1.5 minutes, use 500 microliters of methanol for capping reaction for 30 minutes, cut off the protecting group of tyrosine, add activated 1.6 mmol Two amino acids N-fluorenylmethoxycarbonyl-N'-tert-butoxycarbonyl-L-lysine were reacted for 1 hour, the protective group of lysine was cut off, and 1.6 mmol of activated third amino acid N-fluorenylmethyl was added Oxycarbonyl-N'-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl-L-lysine was reacted for 1 hour, and the protecting group of lysine was cut off, Add activated 1.6 mmol of the fourth amino acid N-fluorenylmethoxycarbonyl-L-phenylalanine and react for 1 hour, cut off the protecting group of phenylalanine, add activated 1.6 mmol of the f...
Embodiment 3
[0069] Testing Experiment of Mechanical Properties of Supramolecular Hydrogel Materials
[0070] Figure 11 It is the sixth pure compound P in Example 2 6 The dynamic frequency scanning spectrum of the storage modulus (G') and loss modulus (G") of the formed supramolecular hydrogel nanomaterials. Figure 12 It is the sixth pure compound P in Example 2 6 Stress scanning patterns of the storage modulus (G') and loss modulus (G") of the formed supramolecular hydrogel nanomaterials. By Figure 11 As can be seen from the square curve c of storage modulus varying with frequency and the dotted curve d of loss modulus varying with frequency, the supramolecular hydrogel nanomaterial prepared by the method of the present invention has a frequency sweep range of 0.1 Hz to 10 Hertz, the value of the storage modulus (G') is always greater than the loss modulus (G"), indicating that the obtained material is a supramolecular hydrogel material. By Figure 12 As can be seen from the square...
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