Li Ke, Li Di, Zhao Li, Chang Yonghe, Zhang Yi, Cui Yan, Zhang Zhiyu
Department of Orthopedics, The Fourth Affiliated Hospital of China Medical University, 4 Chongshandong Road, Shenyang 110032, People's Republic of China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, People's Republic of China.
Bioact Mater. 2020 Jun 12;5(3):721-731. doi: 10.1016/j.bioactmat.2020.04.010. eCollection 2020 Sep.
The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pH-responsive drug delivery systems in cancer therapy. In this work, we designed a calcium carbonate (CaCO)-core-crosslinked nanoparticle of methoxy poly(ethylene glycol)--poly(l-glutamic acid) through mineralization for intracellular delivery of doxorubicin (DOX), referred to as NP/DOX. NP/DOX exhibited high drug loading capability, uniform nanoparticle size, and pH-dependent DOX release. In the meantime, the enhanced cell uptake, superior cytotoxicity toward mouse osteosarcoma K7 cells, extended circulation half-life, and improved accumulation of DOX in K7 allograft tumor from NP/DOX were also demonstrated. More interestingly, NP/DOX displayed improved antitumor effect and reduced side effects against the K7 osteosarcoma-allografted mouse model and the 143B orthotopic osteosarcoma mouse model. Given the superior properties of Ca-mineralized polypeptide nanoparticle for intracellular drug delivery, the smart drug delivery system showed strong competitiveness in clinical chemotherapy of cancers.
肿瘤组织和细胞的酸性微环境为癌症治疗中pH响应性药物递送系统的发展提供了契机。在这项工作中，我们通过矿化设计了一种以碳酸钙（CaCO）为核交联的甲氧基聚（乙二醇）-聚（L-谷氨酸）纳米颗粒，用于阿霉素（DOX）的细胞内递送，称为NP/DOX。NP/DOX表现出高载药能力、均匀的纳米颗粒尺寸以及pH依赖性的DOX释放。同时，还证明了NP/DOX对小鼠骨肉瘤K7细胞具有增强的细胞摄取、优异的细胞毒性、延长的循环半衰期以及在K7同种异体移植瘤中DOX积累的改善。更有趣的是，NP/DOX对K7骨肉瘤同种异体移植小鼠模型和143B原位骨肉瘤小鼠模型显示出改善的抗肿瘤效果和降低的副作用。鉴于钙矿化多肽纳米颗粒在细胞内药物递送方面的优异性能，这种智能药物递送系统在癌症临床化疗中表现出强大的竞争力。
