Preparation of elemene-loaded mesoporous silica nanoparticles and its targeted anti-tumor activity [聚多巴胺修饰的载榄香烯介孔二氧化硅纳米粒的制备及其靶向抗肿瘤活性研究]

作者：Sheng X.-D.; Liu Z.; Luo Y.-X.; Wang X.; Xu M.-J.; Yan H.; Xie T.

来源：Chinese Traditional and Herbal Drugs, 2020, 51(10): 2745-2754.

DOI：10.7501/j.issn.0253-2670.2020.10.016

• Antitumor activity
• Apoptosis
• Elemene
• Grafting rate
• HPLC
• Human embryonic fibroblast HELF cells
• Human lung cancer A549 cells
• In vitro release
• Mesoporous silica
• Mitochondrial membrane potential
• Nanoparticles
• PH-responsive
• Polymerization method
• Quality evaluation
• Solution adsorption method
• Thermogravimetric analysis
• Tumor-targeted delivery

Objective: To prepare polydopamine-modified elemene-loaded mesoporous silica nanoparticles (D/MSN-ELE), and conduct research on formulation process optimization, quality evaluation, in vitro release, in vitro antitumor activity, and ability to promote apoptosis. Methods: Elemene-loaded mesoporous silica nanoparticles (MSN-ELE) were prepared by solution adsorption method, D/MSN-ELE and polydopamine-modified mesoporous silica nanoparticles (D/MSN) were prepared by polymerization. The morphology of the nanoparticles was characterized by transmission electron microscopy. The PDA graft ratio was calculated by thermogravimetric analysis. The loading and encapsulation efficiency of D/MSN-ELE were evaluated using HPLC, the dialysis bag method was used to investigate the release characteristics in vitro of D/MSN-ELE. MTT staining was used to analyze the cytotoxicity of different nanoparticles on HELF and A549 cells. Flow cytometry was used to detect the levels of D/MSN-ELE reactive oxygen species and mitochondrial membrane potential. Results: The optimal preparation process was the drug loading ratio of 6:1, the temperature was 50℃, and the time was 8 h. The D/MSN-ELE prepare under the process condition have a were uniform distribution with a particle size of (288.70 ± 3.88) nm. The average drug loading and encapsulation efficiency were (11.58 ± 0.73)% and (59.82 ± 0.57)%, respectively. In vitro drug release was pH-responsive, and cumulative drug release increased with decreasing pH. The half-lethal concentrations of ELE, MSN-ELE and D/MSN-ELE on A549 cells were 91.29, 27.56 and 6.02 μg/mL, respectively. The detection results of reactive oxygen species and mitochondrial membrane potential further indicated that drug-loaded nanoparticles were able to promote tumor target cell apoptosis. Conclusion: D/MSN-ELE under the optimized process has a higher drug loading, pH-responsive drug release and greatly enhanced antitumor activity. This study provides further experiments basis for tumor-targeted delivery of elemene drugs based on mesoporous silica nanoparticles.

• 单位
  杭州师范大学