Polydopamine-Based Surface Modification of Novel Nanoparticle-Aptamer Bioconjugates for In Vivo Breast Cancer Targeting and Enhanced Therapeutic Effects.
Polydopamine-Based Surface Modification of Novel Nanoparticle-Aptamer Bioconjugates for In Vivo Breast Cancer Targeting and Enhanced Therapeutic Effects.
复制标题
基于聚多巴胺的新型纳米颗粒-适体生物缀合物的表面修饰，用于体内乳腺癌靶向和增强治疗效果
作者：
Tao W;Zeng X;Wu J;Zhu X;Yu X;Zhang X;Zhang J;Liu G;Mei L
在这项研究中，我们报告了一个简单的聚多巴胺（pD）为基础的表面修饰方法，以制备新型的纳米粒子-适配体生物共轭物（Apt-pD-DTX/NPs）在体内肿瘤靶向和增强乳腺癌的治疗效果。新型功能化Apt-pD-DTX/NPs的制备工艺简单，可最大限度地提高肿瘤部位的局部有效药物浓度，提高治疗效果，减少副作用。多巴胺聚合和适体缀合几乎不改变纳米颗粒的特性。体外细胞实验（即荧光纳米颗粒的内吞作用、体外细胞靶向和细胞毒性测定）和体内动物研究（即纳米颗粒的体内成像、生物分布和抗肿瘤作用）均证明，与临床泰索帝®和未经功能修饰的纳米颗粒相比，Apt-pD-DTX/纳米颗粒可实现显著高的靶向效率和增强的治疗效果。最重要的是，Apt-pD-DTX/NPs作为一种有前途的纳米制剂在体内乳腺癌治疗中显示出巨大的潜力，并且构建pD修饰的NP-aptamer生物缀合物在医学应用中可能具有巨大的价值。
In this study, we reported a simple polydopamine (pD)-based surface modification method to prepare novel nanoparticle-aptamer bioconjugates (Apt-pD-DTX/NPs) for in vivo tumor targeting and enhanced therapeutic effects of breast cancer. With simple preparation procedures, the new functionalized Apt-pD-DTX/NPs could maximumly increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. The dopamine polymerization and aptamer conjugation barely changed the characters of NPs. Both in vitro cell experiments (i.e. endocytosis of fluorescent NPs, in vitro cellular targeting and cytotoxicity assays) and in vivo animal studies (i.e. in vivo imaging, biodistribution and antitumor effects of NPs) demonstrated that the Apt-pD-DTX/NPs could achieve significantly high targeting efficiency and enhanced therapeutic effects compared with clinical Taxotere® and NPs without functional modification. Above all, the Apt-pD-DTX/NPs showed great potential as a promising nanoformulation for in vivo breast cancer therapy and the construction of pD-modified NP-aptamer bioconjugates could be of great value in medical use.