Core-Shell Hollow Microspheres of Magnetic Iron Oxide@Amorphous Calcium Phosphate: Synthesis Using Adenosine 5′-Triphosphate and Application in pH-Responsive Drug Delivery

Drug nanocarriers with magnetic targeting and pH-responsive drug-release behavior are promising for applications in controlled drug delivery. Magnetic iron oxides show excellent magnetism, but their application in drug delivery is limited by low drug-loading capacity and poor control over drug release. Herein, core-shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate (MIO@ACP) were prepared and investigated as magnetic, pH-responsive drug nanocarriers. Hollow microspheres of magnetic iron oxide (HMIOs) were prepared by etching solid MIO microspheres in hydrochloric acid/ethanol solution. After loading a drug into the HMIOs, the drug-loaded HMIOs were coated with a protective layer of ACP by using adenosine 5-triphosphate (ATP) disodium salt (Na(2)ATP) as stabilizer, and drug-loaded core-shell hollow microspheres of MIO@ACP (HMIOs/drug/ACP) were obtained. The as-prepared HMIOs/drug/ACP drug-delivery system exhibits superparamagnetism and pH-responsive drug-release behavior. In a medium with pH7.4, drug release was slow, but it was significantly accelerated at pH4.5 due to dissolution of the ACP shell. Docetaxel-loaded core-shell hollow microspheres of MIO@ACP exhibited high anticancer activity.