Lipid-Coated CaCO 3 Nanoparticles as a Versatile pH-Responsive Drug Delivery Platform to Enable Combined Chemotherapy of Breast Cancer.

The development of smart drug delivery nanocarriers for tumor-targeted delivery and controllable release of therapeutic agents is appealing to achieve effective cancer chemotherapy. We herein use CaCO 3 nanoparticles as the core to load doxorubicin (DOX) and direct the assembly of amphiphilic oxaliplatin prodrugs (Pt(IV)) in the presence of other commercial lipids. The obtained DOX-Pt(IV)-CaCO 3 -PEG with excellent physiological stability exhibits instant pH-responsive degradation, thus enabling efficient pH-dependent release of DOX. Via detailed pharmacokinetic study, it is shown that DOX-Pt(IV)-CaCO 3 -PEG shows significantly improved pharmacokinetic behaviors compared to these free drugs, featured in prolonged blood circulation time and superior tumor homing efficacy. Resultantly, treatment with systemic administration of DOX-Pt(IV)-CaCO 3 -PEG was the most effective in suppressing the growth of tumors in Balb/c mice. This study highlights that our liposomal CaCO 3 is a robust and biocompatible platform for preparing pH-responsive drug delivery systems, due to its multifaceted drug loading capacity, and thus is promising for potential clinical translation.