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 pHresponsive drug delivery systems in cancer therapy.In this work,we designed a calcium carbonate(CaCO3)-corecrosslinked 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.