Lim Cheol Won, Kim Dukjoon
School of Chemical Engineering, Sungkyunkwan University, Suwon, Kyunggi 440-746, Republic of Korea.
Biomater Sci. 2021 Mar 10;9(5):1660-1667. doi: 10.1039/d0bm01473g.
Nanoparticles with bone targeting ability and pH-sensitivity were prepared with polyaspartamide (PASPAM) derivatives based on polysuccinimide (PSI) grafted with octadecylamine (C18), hydrazine (HYD) and polyethylene glycol (PEG, Mw: 5000). For the bone targeting, alendronate (ALN), which has bone affinity, was grafted to PEG and doxorubicin (DOX) was conjugated with linkers of acid sensitive hydrazone bonds, which can be cleaved most effectively in an intracellular acidic environment. At pH 5.0, ∼75% of the drug was released from ALN-PEG/C18/HYD-DOX-g-PASPAM due to the effective cleavage of HYD under the acidic condition. Also, ALN-PEG/C18/HYD-DOX-g-PASPAM particles were more effectively adsorbed on the surface of bone than PEG/C18/HYD-DOX-g-PASPAM. According to an in vivo antitumor activity test, the volume of tumor treated with ALN-PEG/C18/HYD-DOX-g-PASPAM decreased (1550 mm3) when compared with the PBS control sample (3850 mm3), proving that ALN-PEG/C18/HYD-DOX-g-PASPAM is an effective drug delivery system for the treatment of bone metastasis of breast cancer.
基于接枝了十八胺（C18）、肼（HYD）和聚乙二醇（PEG，分子量：5000）的聚琥珀酰亚胺（PSI）制备了具有骨靶向能力和pH敏感性的纳米颗粒。为实现骨靶向，将具有骨亲和性的阿仑膦酸盐（ALN）接枝到PEG上，并将阿霉素（DOX）与酸敏感腙键连接子共轭，该连接子在细胞内酸性环境中能最有效地裂解。在pH 5.0时，由于酸性条件下HYD的有效裂解，约75%的药物从ALN-PEG/C18/HYD-DOX-g-PASPAM中释放出来。此外，ALN-PEG/C18/HYD-DOX-g-PASPAM颗粒比PEG/C18/HYD-DOX-g-PASPAM更有效地吸附在骨表面。根据体内抗肿瘤活性试验，与PBS对照样品（3850 mm³）相比，用ALN-PEG/C18/HYD-DOX-g-PASPAM治疗的肿瘤体积减小（1550 mm³），证明ALN-PEG/C18/HYD-DOX-g-PASPAM是治疗乳腺癌骨转移的有效药物递送系统。
