In situ mineralization of anticancer drug into calcium carbonate monodisperse nanospheres and their pH-responsive release property

• Monodisperse calcium carbonate nanospheres (~ 200 nm) encapsulated with doxorubicin was prepared.
• The preparation of CaCO3 nanospheres and the encapsulation of doxorubicin were facilitated in one step.
• Our strategy is a facile precipitation method for encapsulation of anticancer drug in water without any other organic agent.
• The release of doxorubicin from the nanospheres is pH responsive.

In this paper, we facilitated the preparation of uniform calcium carbonate nanospheres and the encapsulation of anticancer drug (Doxorubicin, Dox) in one step by a facile bio-inspired mineralization method at room temperature. Hesperidin (Hesp), a natural originated flavanone glycoside, was introduced as crystallization modifier. The obtained Dox encapsulated CaCO3 nanospheres (Dox@CaCO3-Hesp NSs) having a narrow size range of ~ 200 nm. The drug loading/release studies reveal that these Dox@CaCO3-Hesp NSs have a drug loading efficiency (DLE) of 83% and drug loading content (DLC) of 14 wt%. Besides, the release of Dox from Dox@CaCO3-Hesp NSs was pH depended. At pH = 7.4, only a small amount (~ 28%) of Dox was released. While at pH = 5.0, all amount of incorporated Dox was released. Confocal laser scanning microscopy (CLSM) image reveals the Dox@CaCO3-Hesp NSs can internalize the cells. These results suggest the Dox@CaCO3-Hesp NSs can be potentially used to utilize pH-responsive delivery of anticancer drugs.