Institute of Medicine and Health, Guangdong Academy of Sciences, National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Material Products, Guangdong Institute of Medical Instruments, Guangzhou 510500, China; Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Int J Pharm. 2021 Jan 5;592:120020. doi: 10.1016/j.ijpharm.2020.120020. Epub 2020 Oct 27.
Green tea extract epigallocatechin-3-gallate (EGCG), as a kind of natural active compounds, has become a research hotspot in cancer treatment. However, poor stability, low bioavailability and antitumor efficacy limit the application of EGCG. In this study, mesoporous dopamine (MPDA) with high drug loading and good biocompatibility loaded EGCG, garlic extract diallyl trisulfide (DATS) and photosensitizer (indocyanine green, ICG) by π-π stacking and hydrophobic-hydrophobic interaction, and the nano-system involved filling the mesoporous of the MPDA with phase change material (1-tetradecanol, 1-TD) molecules, which acted as a thermosensitive gatekeeper. The results indicated that MPDA-ICG@TD has an excellent photothermal effect and good stability. Due to the solid-liquid phase transition characteristics of the phase change material, MPDA-ICG@TD could control the release of drugs under near-infrared laser irradiation. Besides, cytotoxicity and apoptosis experiments showed that MPDA-ICG/EGCG/DATS@TD could be efficiently inhibited 4T1 cell proliferation and accelerate cell apoptosis than use diallyl trisulfide or EGCG alone, which means that the combination of natural active compounds EGCG and diallyl trisulfide has excellent synergy and can effectively improve the antitumor effect of EGCG. Moreover, this nano-system exhibited non-toxicity and good blood compatibility. This study provides a promising and effective strategy for improving the antitumor efficacy of natural active compound EGCG.
绿茶提取物表没食子儿茶素-3-没食子酸酯（EGCG）作为一种天然活性化合物，已成为癌症治疗的研究热点。然而，其较差的稳定性、低生物利用度和抗肿瘤疗效限制了 EGCG 的应用。本研究通过π-π堆积和疏水-疏水相互作用，将载药量高、生物相容性好的介孔多巴胺（MPDA）负载 EGCG、大蒜提取物二烯丙基三硫化物（DATS）和光敏剂（吲哚菁绿，ICG），并将相变材料（十四醇，1-TD）分子填充到 MPDA 的介孔中，充当热敏门卫。结果表明，MPDA-ICG@TD 具有优异的光热效应和良好的稳定性。由于相变材料的固-液相转变特性，MPDA-ICG@TD 可以在近红外激光照射下控制药物的释放。此外，细胞毒性和细胞凋亡实验表明，MPDA-ICG/EGCG/DATS@TD 能有效抑制 4T1 细胞的增殖，并促进细胞凋亡，其效果优于单独使用二烯丙基三硫化物或 EGCG，这意味着天然活性化合物 EGCG 和二烯丙基三硫化物的联合具有优异的协同作用，能有效提高 EGCG 的抗肿瘤效果。此外，该纳米体系表现出无毒和良好的血液相容性。本研究为提高天然活性化合物 EGCG 的抗肿瘤效果提供了一种有前景且有效的策略。
