目的 制备白藜芦醇pH敏感介孔二氧化硅纳米粒（Res-pH-MSNs），并进行体外抗肿瘤活性研究。方法 以包封率、载药量和粒径为指标，单因素试验结合Box-Behnken设计–效应面法优化Res-pH-MSNs处方工艺。X射线衍射法分析晶型，扫描电镜观察形貌，并测试pH敏感性。采用噻唑蓝法考察Res-pH-MSNs对子宫内膜癌HEC-1-A细胞的体外抗肿瘤活性。采用Annexin V-FITC/PI双染法考察Res-pH-MSNs对子宫内膜癌HEC-1-A细胞凋亡的影响。结果 Res-pH-MSNs最佳处方为：介孔二氧化硅纳米粒与药物质量比为1.95∶1.00，壳聚糖质量分数为0.19%，制备时间为12.50 h。Res-pH-MSNs平均包封率、载药量、粒径和Zeta电位分别为（84.96±1.17）%、（22.58±0.66）%、（137.28±7.69）nm和（31.09±0.87）mV。Res-pH-MSNs呈规则球形，白藜芦醇在Res-pH-MSNs中以无定型形式存在，体外释药具有明显的pH值敏感性。Res-pH-MSNs可有效抑制HEC-1-A细胞增殖，24、48 h的半数抑制浓度（IC₅₀）分别为47.72、28.82 μg/mL，并有效诱导细胞凋亡。结论 制备的Res-pH-MSNs具有良好pH值敏感性和抗肿瘤活性。

Objective To prepare resveratrol pH-sensitive mesoporous silica nanoparticles (Res-pH-MSNs), and to investigate its antitumor activity in vitro. Methods Encapsulation efficiency, drug loading, and particle size were acted as evaluation indexes, Res-pH-MSNs formulation was optimized though single factor test and Box-Behnken design-response surface method. Crystal form of Res-pH-MSNs was analyzed by X-ray diffraction, scanning electron microscope was used to observe the morphology of Res-pH-MSNs, and the pH-sensitivity was also checked. Inhibitory effects of Res-pH-MSNs on endometrial cancer HEC-1-A cells were detected by methyl thiazolyl tetrazolium (MTT) method. The effects on apoptosis in HEC-1-A cells was detected using Annexin V- FITC/PI double staining method. Results Optimal formulation of Res-pH-MSNs was as following: MSNs to drug ratio was 1.95:1.00, chitosan concentration was 0.19%, and preparation time was 12.50 h. Average envelopment efficiency, drug loading, particle size, and Zeta potential were (84.96 ± 1.17) %, (22.58 ± 0.66) %, (137.28 ± 7.69) nm, and (31.09 ± 0.87) mV, respectively. Res-pH-MSNs were regular spherical, resveratrol existed as an amorphous form in the Res-pH-MSNs, and drug release in vitro had obvious pH-sensitivity. Res-pH-MSNs significantly inhibited the proliferation of HEC-1-A cells with half-maximal inhibitory concentration (IC₅₀) of 47.72 and 28.82 μg/mL at 24 and 48 h, respectively, and effectively induced apoptosis of HEC-1-A cells. Conclusion The prepared Res-pH-MSNs have obvious pH-sensitivity and antitumor activity.

R944

河南省科技攻关项目（252102310468）；河南省高等学校重点科研项目计划（23B320013）；河南应用技术职业学院2023年度校级课题（2023-KJ-54）