目的 制備白藜蘆醇pH敏感介孔二氧化硅納米粒（Res-pH-MSNs），并進(jìn)行體外抗腫瘤活性研究。方法 以包封率、載藥量和粒徑為指標(biāo)，單因素試驗(yàn)結(jié)合Box-Behnken設(shè)計(jì)–效應(yīng)面法優(yōu)化Res-pH-MSNs處方工藝。X射線衍射法分析晶型，掃描電鏡觀察形貌，并測試pH敏感性。采用噻唑藍(lán)法考察Res-pH-MSNs對子宮內(nèi)膜癌HEC-1-A細(xì)胞的體外抗腫瘤活性。采用Annexin V-FITC/PI雙染法考察Res-pH-MSNs對子宮內(nèi)膜癌HEC-1-A細(xì)胞凋亡的影響。結(jié)果 Res-pH-MSNs最佳處方為：介孔二氧化硅納米粒與藥物質(zhì)量比為1.95∶1.00，殼聚糖質(zhì)量分?jǐn)?shù)為0.19%，制備時(shí)間為12.50 h。Res-pH-MSNs平均包封率、載藥量、粒徑和Zeta電位分別為（84.96±1.17）%、（22.58±0.66）%、（137.28±7.69）nm和（31.09±0.87）mV。Res-pH-MSNs呈規(guī)則球形，白藜蘆醇在Res-pH-MSNs中以無定型形式存在，體外釋藥具有明顯的pH值敏感性。Res-pH-MSNs可有效抑制HEC-1-A細(xì)胞增殖，24、48 h的半數(shù)抑制濃度（IC₅₀）分別為47.72、28.82 μg/mL，并有效誘導(dǎo)細(xì)胞凋亡。結(jié)論 制備的Res-pH-MSNs具有良好pH值敏感性和抗腫瘤活性。

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

河南省科技攻關(guān)項(xiàng)目（252102310468）；河南省高等學(xué)校重點(diǎn)科研項(xiàng)目計(jì)劃（23B320013）；河南應(yīng)用技術(shù)職業(yè)學(xué)院2023年度校級課題（2023-KJ-54）