Dai Yu, Xing Han, Song Fuling, Yang Yue, Qiu Zhixia, Lu Xiaoyu, Liu Qi, Ren Shuangxia, Chen Xijing, Li Ning
Clinical Pharmacokinetics Research Room, School of Basic Medicine and Clinical Pharmacy, Nanjing, Jiangsu Province 210009, China.
Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu Province 210009, China.
J Pharm Sci. 2016 Sep;105(9):2949-2958. doi: 10.1016/j.xphs.2016.03.038. Epub 2016 May 18.
Multilayer nanoparticle combining the merits of liposome and polymer nanoparticle has been designed for the targeted delivery of doxorubicin (DOX) in cancer treatment. In this study, DOX-PLGA-lecithin-PEG-biotin nanoparticles (DOX-PLPB-NPs) were fabricated and functionalized with biotin for specific tumor targeting. Under the transmission electron microscopy observation, the lipid layer was found to be coated on the polymer core. The physical characteristics of PLPB-NPs were also evaluated. The confocal laser scanning microscopy confirmed the cellular uptake of nanoparticles and targeted delivery PLPB-NPs. The in vitro release experiment demonstrated a pH-depending release of DOX from drug-loaded PLPB-NPs. Cytotoxicity studies in HepG2 cells and in vivo antitumor experiment in tumor-bearing mice both proved DOX-PLPB-NPs showed the best inhibition effect of tumor proliferation. In biodistribution studies, DOX-PLPB-NPs showed a higher DOX concentration than free DOX and DOX-PLGA-lecithin-PEG nanoparticles (DOX-PLP-NPs) in tumor site, especially in 24 h, and the lowest DOX level in normal organs. The results were coincident with the strongest antitumor ability showed among in vivo antitumor experiment. Histopathology analysis demonstrated that DOX-PLPB-NPs exhibited the strongest antitumor ability and lowest cardiotoxicity. In brief, the PLPB-NPs were proved to be an efficient delivery system for tumor-targeting treatment.
结合脂质体和聚合物纳米颗粒优点的多层纳米颗粒已被设计用于在癌症治疗中靶向递送阿霉素（DOX）。在本研究中，制备了阿霉素-聚乳酸-羟基乙酸共聚物-卵磷脂-聚乙二醇-生物素纳米颗粒（DOX-PLPB-NPs），并用生物素进行功能化修饰以实现对特定肿瘤的靶向作用。在透射电子显微镜观察下，发现脂质层包覆在聚合物核上。还对PLPB-NPs的物理特性进行了评估。共聚焦激光扫描显微镜证实了纳米颗粒的细胞摄取以及PLPB-NPs的靶向递送。体外释放实验表明，载药PLPB-NPs中阿霉素的释放具有pH依赖性。在HepG2细胞中的细胞毒性研究以及在荷瘤小鼠中的体内抗肿瘤实验均证明，DOX-PLPB-NPs对肿瘤增殖的抑制效果最佳。在生物分布研究中，DOX-PLPB-NPs在肿瘤部位的阿霉素浓度高于游离阿霉素和阿霉素-聚乳酸-羟基乙酸共聚物-卵磷脂-聚乙二醇纳米颗粒（DOX-PLP-NPs），尤其是在24小时时，并且在正常器官中的阿霉素水平最低。该结果与体内抗肿瘤实验中显示的最强抗肿瘤能力一致。组织病理学分析表明，DOX-PLPB-NPs表现出最强的抗肿瘤能力和最低的心脏毒性。简而言之，PLPB-NPs被证明是一种用于肿瘤靶向治疗的有效递送系统。
