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

Zheng Cai,Zhimei He,Li-Ping Jiang,Yuezhu Chen,Xiaoge Wu,Yingwen Zhang

doi:10.1039/c9ra07894k

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.

Highlights

Cancer has become a major threat to human beings due to its high incidence, severe mortality, and low survival rate
A biodegradable nanocarrier based on an acid-sensitive calcium phosphate/silica dioxide (CAP/SiO2) composite was constructed for the codelivery of drug and small interfering RNA (siRNA)
CAP/SiO2 showed only one hump peak and a small peak located at about 31 degree, indicating that CAP has been incorporated into the skeleton of SiO2 during the synthesis process.[13,18]

Summary

Introduction

Cancer has become a major threat to human beings due to its high incidence, severe mortality, and low survival rate. A biodegradable nanocarrier based on an acid-sensitive calcium phosphate/silica dioxide (CAP/SiO2) composite was constructed for the codelivery of drug and siRNA. The release amount reached to 67% a er DOX-loaded CAP/SiO2 dispersed in pH 5.0 for 48 h compared to that of 20% in pH 7.4 buffer solution, indicating good stability in a physiological environment.

Results

Conclusion