A comparative study of polydopamine modified and conventional chemical synthesis method in doxorubicin liposomes form the aspect of tumor targeted therapy
A comparative study of polydopamine modified and conventional chemical synthesis method in doxorubicin liposomes form the aspect of tumor targeted therapy
复制标题
DOI：
10.1016/j.ijpharm.2019.01.033
复制
发表时间：
2019-03-25
影响因子：
5.8
通讯作者：
Han, Meihua
中科院分区：
文献类型：
--
作者：
Bi, Dongdong;Zhao, Lei;Han, Meihua
聚多巴胺（PDA）是一种简单、新颖、用途广泛的制备靶向纳米粒子的方法，它可以作为一个平台将靶向配体偶联到无反应性化学基团的聚合物载体上。为了更好地了解新型PDA方法与传统化学合成方法的差异，我们利用上述方法制备了两种叶酸（FA）靶向脂质体，并负载了阿霉素（DOX）。FA-PDA-DOX脂质体和DOX-FA脂质体分别代表PDA和常规方法。FA-PDA-DOX脂质体比DOX-FA脂质体粒径小，且稳定性好，形态呈球形，对HeLa细胞抑制作用强，在肿瘤部位药物蓄积高。两种靶向脂质体在体外细胞毒性研究和体内生物分布试验中均无显著差异。而只有FA-PDA-DOX脂质体表现出ph敏感性，这与PDA层有关，能更好地控制药物释放。与DOX-FA脂质体相比，FA-PDA-DOX脂质体在体内抗肿瘤实验中更安全，抑制率仍在70%以上。本研究表明，该方法可以以更简单、更安全的方式达到与传统方法相似的治疗水平，是未来药物输送系统中有用的、有前途的纳米载体。
Polydopamine (PDA) has been a simple, novel and versatile method to prepare targeted nanoparticles, which can be used as a platform for conjugating targeted ligands to polymer carriers without reactive chemical groups. To better understand the difference between the novel PDA method and conventional chemical synthesis way, we developed two kinds of folate (FA)-targeted liposomes loaded doxorubicin (DOX) by the above methods. FA-PDA-DOX liposomes and DOX-FA liposomes represented PDA and conventional method, respectively. FA-PDA-DOX liposomes had a smaller particle size than DOX-FA liposomes, and both of them presented good stability, spherical morphology, strong inhibition effect to HeLa cells and high drug accumulation in the tumor site. There were no significant differences between the two targeted liposomes in the in vitro cytotoxicity study and in vivo bio-distribution assay. While only FA-PDA-DOX liposomes showed pH-sensitive properties, which was attributed to the PDA layers and can control the drug release better. Compared to DOX-FA liposomes, FA-PDA-DOX liposomes were much safer in an antitumor experiment in vivo, and the inhibition rate was still over 70%. This study demonstrated the PDA method could achieve therapeutic levels similar to traditional methods in a simpler and safer way, which can be useful and promising nanocarriers for drug delivery system in the future.