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

Li, Ke; Li, Di; Zhao, Li; Chang, Yonghe; Zhang, Yi; Cui, Yan; Zhang, Zhiyu · Bioact Mater · 2020

basic_science · Level V

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Abstract

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<sub>3</sub>)-core-crosslinked nanoparticle of methoxy poly(ethylene glycol)-<i>block</i>-poly(l-glutamic acid) through mineralization for intracellular delivery of doxorubicin (DOX), referred to as <sup>Ca</sup>NP/DOX. <sup>Ca</sup>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 <sup>Ca</sup>NP/DOX were also demonstrated. More interestingly, <sup>Ca</sup>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.