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

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.