Triple negative breast cancer has a high local recurrence rate and poor prognosis, which seriously threatens women's health. It is urgent to find a new strategy to effectively prevent progressive disease. The intelligent drug delivery system based on new biomedical materials can play a vital role in the comprehensive and synergistic treatment of the disease. In this study, sunitinib nanoparticles were prepared by solvent precipitation. A new enzyme responsive hydrogel was well prepared after loading the nano-drug into it by Michael addition reaction. Then the novel hydrogel was identified and characterized by transmission electron microscope, stability test, and drug dissolution test. Furthermore, the anti-tumor and anti-recurrence effects of the hydrogel was evaluated by function tests both in vitro and in vivo. Finally, the preliminary biosafety evaluation of the hydrogel was performed. The results indicate that the enzyme responsive hydrogel loading sunitinib nanoparticles was successfully prepared. The physicochemical properties of the new hydrogel showed good stability. The particle size of nano-sunitinib was about 400 nm. The dissolution curves showed that sunitinib nanoparticles could release continuously from the hydrogel, and the release efficiency was higher under the exposing of matrix metalloproteinase-2; functional tests showed that the hydrogel exhibited a good anti-tumor effect in vitro, showing a good biological function to promote apoptosis and prevent recurrence in vivo; the biosafety of the hydrogel in vivo was evaluated and showed no obvious toxicity, mice were well tolerated. Such a therapy strategy may inhibit the local recurrence and improve the clinical benefit of patients.
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