State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, PR China; Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, PR China.
State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, PR China; Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, PR China.
Colloids Surf B Biointerfaces. 2019 Jun 1;178:263-268. doi: 10.1016/j.colsurfb.2019.03.002. Epub 2019 Mar 2.
Ammonium bicarbonate (ABC) liposomes can only release drugs extracellularly while intracellular drug delivery could be more promising than extracellular release in chemotherapy. The purpose of this work was to endow the ABC liposomes with tumor-triggered targeting effect, to realize the intracellular drug release and retain the long circulation characteristics of the liposomes. The tumor-triggered targeting ABC (TT-ABC) liposomes were proposed to improve uptake of tumor cells owing to folate (FA) - specific binding. To retain the long circulation characteristics of the TT-ABC liposomes, we synthesized PEGylated phospholipid with a pH-sensitive imine bond (DSPE-PEG) and added it to the liposomes. After endocytosis by tumor cells via active targeting, the TT-ABC liposomes produced carbon dioxide (CO) bubbles at elevated temperature or in the acidic endo/lysosome. The permeable defects could be created in the phospholipid bilayer by the generating CO bubbles, so the liposomes could quickly release the drugs intracellularly. Doxorubicin (DOX) loaded TT-ABC (DOX@TT-ABC) liposomes exhibited good stability at physiological pH (7.4) and released DOX quickly at reduced pH (6.4) and hyperthermia (42 °C). DOX@TT-ABC liposomes showed significantly enhanced cellular uptake, intracellular accumulation of DOX, and cytotoxicity at pH 6.4 and 42 °C.
碳酸氢铵（ABC）脂质体只能将药物释放到细胞外，而细胞内药物递送可能比细胞外释放更有前途。这项工作的目的是赋予 ABC 脂质体肿瘤触发靶向效应，实现细胞内药物释放，并保持脂质体的长循环特性。提出肿瘤触发靶向 ABC（TT-ABC）脂质体由于叶酸（FA）特异性结合而提高肿瘤细胞的摄取。为了保持 TT-ABC 脂质体的长循环特性，我们合成了具有 pH 敏感亚胺键的聚乙二醇化磷脂（DSPE-PEG）并将其添加到脂质体中。通过主动靶向作用被肿瘤细胞内吞后，TT-ABC 脂质体在高温或酸性内体/溶酶体中产生二氧化碳（CO）气泡。生成的 CO 气泡可在磷脂双层中产生可渗透的缺陷，从而使脂质体能够快速将药物释放到细胞内。载多柔比星（DOX）的 TT-ABC（DOX@TT-ABC）脂质体在生理 pH（7.4）下表现出良好的稳定性，在降低的 pH（6.4）和高温（42°C）下迅速释放 DOX。在 pH 6.4 和 42°C 下，DOX@TT-ABC 脂质体显示出显著增强的细胞摄取、DOX 的细胞内积累和细胞毒性。
