目的 制備載姜黃素的透明質酸-熊果酸-硫辛酸交聯(lián)納米粒（Cur/cLA-HU NPs），并進行體外抗腫瘤活性評價。方法 以載藥量、包封率為指標，采用超聲法，通過單因素考察優(yōu)化Cur/cLA-HU NPs的制備工藝，并對Cur/cLA-HU NPs的粒徑、Zeta電位、形態(tài)和體外釋藥情況進行評價。通過熒光倒置顯微鏡分析HepG2細胞對Cur/cLA-HU NPs的攝取，以MTT法考察Cur/cLA-HU NPs對HepG2細胞的毒性。結果 最佳載藥工藝為：以甲醇為藥物姜黃素有機溶劑，以藥質比4∶10進行投料，超聲于100 W下次數(shù)為3次，每次處理3 min，超聲程序設置為開2 s、停4 s。Cur/cLA-HU NPs的包封率為（87.91±1.51）%，載藥量為（16.64±0.45）%，粒徑為（172.3±2.57）nm，PDI為（0.174±0.021），分散均勻，Zeta電位為（−35.3±2.12）mV。Cur/cLA-HU NPs具有還原響應性，釋放藥物的快慢受到GSH濃度的影響；靶向腫瘤細胞，且被細胞快速攝取；對HepG2人肝癌細胞增殖具有明顯抑制作用。結論 Cur/cLA-HU NPs載藥量和包封率高，其體外抗腫瘤活性稍優(yōu)于姜黃素，具有腫瘤靶向性。

Objective To prepare curcumin-loaded hyaluronic acid-ursolic acid-lipoic acid cross-linked nanoparticles (Cur/cLA-HU NPs), and evaluate their antitumor activities in vitro. Methods The preparation process of Cur/cLA-HU NPs was optimized by single-factor method and verification by ultrasound, taking drug load and encapsulation rate as indicators. The particle size, Zeta potential, morphology and in vitro drug release of Cur/cLA-HU NPs were evaluated. The uptake of Cur/cLA-HU NPs by HepG2 cells was qualitatively analyzed by fluorescence inverted microscopy and the cytotoxicity of Cur/cLA-HU NPs to HepG2 cells was investigated by MTT assay. Results The optimal preparation process is as following:methanol was used as the organic solvent of curcumin, the drug mass ratio was 4:10, the number of times of ultrasonic treatment was 3 at 100 W, and each time was treated for 3 min. The ultrasonic program was set to open for 2 s and stop for 4 s. The encapsulation efficiency of Cur/cLA-HU NPs was (87.91 ±1.51)%, drug loading was (16.64 ±0.45)%, particle size was (172.3 ±2.57) nm, PDI was (0.174 ±0.021), dispersion was uniform, and Zeta potential was (−35.3 ±2.12) mV. Cur/cLA-HU NPs exhibit reduction responsiveness, and the speed of drug release was influenced by the concentration of GSH. Cur/cLA-HU NPs target tumor cells and were rapidly up-taken by cells, and had a significant inhibitory effect on the proliferation of HepG2 cells. Conclusion Cur/cLA-HU NPs have high drug load and encapsulation rate, and its anti-tumor activity in vitro is slightly better than curcumin, with tumor targeting.

R944

河北省自然科學基金資助項目（H2021209024）