Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy

作者：Ke Li, Di Li, Zhao Li, Yonghe Chang, Yi Zhang, Yan Cui, Zhiyu Zhang · 发表于：Bioactive Materials · 年份：2020 · DOI：10.1016/j.bioactmat.2020.04.010 · 被引用次数：76 · 研究领域：Nanoparticle-Based Drug Delivery、Bone Tissue Engineering Materials、Graphene and Nanomaterials Applications

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 (CaCO3)-core-crosslinked nanoparticle of methoxy poly(ethylene glycol)-block-poly(l-glutamic acid) through mineralization for intracellular delivery of doxorubicin (DOX), referred to as CaNP/DOX. CaNP/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 CaNP/DOX were also demonstrated. More interestingly, CaNP/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.