新型酶响应型水凝胶合成及其在预防三阴性乳腺癌术后复发研究

Synthesis of novel enzyme responsive hydrogel and its applications in prevention of postoperative recurrence of triple negative breast cancer

应用溶剂—反溶剂法制备舒尼替尼纳米粒,通过迈克尔加成反应将药物装载入水凝胶,即合成新型酶响应型舒尼替尼纳米粒水凝胶;通过扫描电镜、粒径分析、药物溶出率计算等方法对新材料进行鉴定和表征;进一步体内外功能试验评估该材料的抗肿瘤及防复发作用;最后对该材料进行初步安全性评价。实验结果表明,实现了酶响应型舒尼替尼纳米粒水凝胶的成功制备,舒尼替尼纳米粒在水凝胶中分布均匀,粒径约400 nm,稳定性能良好;新材料表现出优异的控缓释作用,在体外抑制肿瘤细胞及血管内皮细胞活性,在体内促进小鼠肿瘤细胞凋亡、阻抑肿瘤复发;局部给药过程中,小鼠耐受性良好,新材料无明显毒副作用。

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.