EDC/NHS–mediated reaction was used to synthesize CMCTS-Tk polymers especially, and amide coupling reaction happened between the carboxylic groups (CMCTS) and the amino groups (NH2-Tk-NH2). In brief, first, 5 g of CMCTS was dissolved in 150 ml of distilled water at 40°C. Simultaneously, 2 g NH2-Tk-NH2 was dissolved in 125 ml buffer solution and 2 g EDC (10 mmol) and 1 g NHS (13.9 mmol) was also added to activate the carboxylic groups of CMCTS. Subsequently, the pH value of the solution stayed at 6.0 after stirring for 1 h. The purification of CMCTS-Tk was divided into two steps. The first step is to remove excess EDC/NHS, the product is placed into a dialysis bag with a molecular cutoff point of 3,500 Da for 3 days to remove the excess EDC and NHS. The second step is to remove the excess or unreacted Tk, the product is placed into a vessel filled with anhydrous acetone under a shaker (200 rpm) for 24 h. The product is washed with anhydrous acetone thrice and with deionized water once. Then 100 mg Cur was added to 10 ml ethyl alcohol solution and then CMCTS-Tk hydrogel (5 g) was placed in a shaker (100 rpm/s) overnight at 40°C to fully loading 48 h. After loading Cur, the excess unloading Cur is taken to measure the concentration for calculating the loading quality into CMCTS-Tk hydrogel via the UV-Vis method. Finally, the Cur@CMCTS-Tk hydrogel was obtained following the process of filtration and lyophilization. In addition, a control group of hydrogel (named Cur@CMCTS) was prepared in which Tk-c [NH2-(CH2)6-NH2] was used to replace NH2-Tk-NH2, and the other steps remained unchanged.

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