National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Acta Biomater. 2018 Apr 1;70:186-196. doi: 10.1016/j.actbio.2018.02.008. Epub 2018 Feb 13.
Intelligent drug delivery systems with prolonged circulation time, reduced drug leakage in blood, target site-triggered drug release and endosomal escape are attractive and ideal for malignant tumor therapy. Herein, doxorubicin (DOX)-conjugated smart polymeric micelles based on 4-carboxy benzaldehyde-grafted poly (L-lysine)-block-poly (methacryloyloxyethyl phosphorylcholine) (PLL(CB/DOX)-b-PMPC) copolymer are prepared. DOX and electronegative 4-carboxy benzaldehyde are conjugated to the PLL block via an imine linkage and as a result, the drug loaded micelles exhibited the pH-triggered charge-conversion property and accelerated drug release at tumor pH. In vitro cytotoxicity studies of these DOX-loaded micelles exhibited great tumor inhibition against HeLa and 4T1 cells. Moreover, in mice models of breast cancer, these DOX-loaded micelles showed better anti-tumor efficacy and less organ toxicity than free drug. In summary, these polymeric micelles could be applied as potential nanocarriers for cancer therapy.
As a typical anti-cancer drug, Doxorubicin (DOX) exhibited remarkable tumor inhibition but was limited by its low drug utilization and strong toxicity to organs. To overcome these challenges, we developed a DOX-conjugated polymeric micelle as a nano drug carrier which was endowed with pH-sensitivity and charge-conversion function. The structure of micelles would quickly disintegrate with surface charge-conversion in acidic environment, which would contribute to the endosomal escape and accelerated drug release. These DOX-conjugated micelles would provide a promising platform for the efficient DOX delivery and better anti-cancer efficiency.
具有延长循环时间、减少血液中药物泄漏、靶向触发药物释放和内体逃逸的智能药物输送系统，对于恶性肿瘤治疗具有吸引力和理想性。本文制备了基于 4-羧基苯甲醛接枝聚 L-赖氨酸-嵌段-聚（甲基丙烯酰氧乙基磷酸胆碱）（PLL（CB/DOX）-b-PMPC）共聚物的阿霉素（DOX）偶联智能聚合物胶束。DOX 和带负电的 4-羧基苯甲醛通过亚胺键偶联到 PLL 嵌段上，因此载药胶束表现出 pH 触发的电荷转换特性，并在肿瘤 pH 下加速药物释放。这些载 DOX 胶束的体外细胞毒性研究显示出对 HeLa 和 4T1 细胞的强大肿瘤抑制作用。此外，在乳腺癌小鼠模型中，这些载 DOX 胶束显示出比游离药物更好的抗肿瘤疗效和更少的器官毒性。总之，这些聚合物胶束可以作为癌症治疗的潜在纳米载体。
作为一种典型的抗癌药物，阿霉素（DOX）表现出显著的肿瘤抑制作用，但由于其药物利用率低和对器官的强烈毒性而受到限制。为了克服这些挑战，我们开发了一种 DOX 偶联的聚合物胶束作为纳米药物载体，具有 pH 敏感性和电荷转换功能。在酸性环境中，胶束的结构会迅速发生解体，表面电荷发生转换，有助于内体逃逸和加速药物释放。这些 DOX 偶联的胶束为高效 DOX 输送和更好的抗癌效率提供了有前途的平台。
