pH-sensitive CAP/SiO2 composite for efficient co-delivery of doxorubicin and siRNA to overcome multiple drug resistance

Abstract

Long-term administration of chemotherapeutic agents often leads to multiple drug resistance (MDR), which greatly impairs the treatment outcome. To overcome this problem, a biodegradable nanocarrier based on an acid-sensitive calcium phosphate/silica dioxide (CAP/SiO₂) composite was constructed for the codelivery of drug and siRNA. Anticancer drug doxorubicin (DOX) was encapsulated into the composite scaffold by interacting with the exposed Ca²⁺ of CAP/SiO₂ to achieve high drug loading (180 μg mg⁻¹). With further decoration of siRNA, the nanocarrier was applied to enhance the therapeutic efficacy by silencing MDR-relevant genes (P-gp) of DOX-resistance K562/ADR cancer cells. Benefiting from the intrinsic acid degradability of CAP/SiO₂, the nanocomposite demonstrated pH-responsive release behavior, favoring drug/siRNA release within acidic endo-/lysosomes. Consequently, due to the drug and gene effects, this biodegradable nanomedicine demonstrated enhanced therapeutic efficiency, providing a novel strategy for cancer therapy.