Lipid-Coated CaCO3 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 CaCO3 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)-CaCO3-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)-CaCO3-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)-CaCO3-PEG was the most effective in suppressing the growth of tumors in Balb/c mice. This study highlights that our liposomal CaCO3 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.