阿霉素
脂质体
化学
胞浆
生物物理学
药物输送
脱镁叶绿酸A
药理学
生物化学
光动力疗法
化疗
医学
酶
生物
有机化学
内科学
作者
Eunyoung Park,Dong‐Hyun Lee,Yeeun Lee,Eunjin Jeong,Se‐Hee Kim,Heebeom Koo
标识
DOI:10.1016/j.colcom.2021.100565
摘要
For successful combination therapy using nanoparticles, stable loading and targeted delivery of different drugs are important. Herein, we prepared pH-sensitive liposomes with hydrophilic doxorubicin (Dox) in the core and hydrophobic pheophobide-a (Pba) in the lipid membrane (pH-lipo-Dox-Pba). The liposomes provided high drug accumulation in tumor tissue, with an enhanced permeability and retention (EPR) effect and enhanced binding to tumor cells by cyclic Arg-Gly-Asp peptide (cRGD). After cellular uptake, Dox was released in response to the endo-lysosomal acidic pH and moved into the nucleus, while Pba remained in the cytosol. Therefore, a double hit strategy composed of a simultaneous attack on nucleus and cytosol could be achieved by chemo- and photodynamic therapy. High tumor accumulation of pH-lipo-Dox-Pba was observed after intravenous injection into 4T1 tumor-bearing mice. Effective suppression of tumor growth in the same mouse model demonstrated a synergetic effect of combination therapy enabled by the double hit strategy using pH-lipo-Dox-Pba.
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