The synthesis of sulfate doped hydroxyapatite for enhanced drug loading and chemotherapeutic drug delivery towards lung cancer treatment

Abstract Tumor-targeting chemotherapeutic drug delivery platforms based on pH stimulus and “smart” drug nanocarriers have received increasing interest in precise control of spatial and temporal drug release to target lung cancer cells and reduce serious side effects compared to conventional cancer chemotherapy. Incorporation of bioactive targeting agent into drug nanocarriers offers new opportunities to improve the targeting specificity and maximize the anti-cancer therapeutic effects. Up to date, there has been limited study on the construction of effective pH-responsive tumor-targeting drug delivery systems based on bioactive targeting agents. Herein, we report the preparation of highly porous sulfate doped HAp (S-HAp) nanospheres via a facile hydrothermal approach, and apply surface-modified S-HAp nanospheres with PEG and folic acid (FA) as novel drug nanocarriers for effective pH-responsive chemotherapeutic drug delivery towards lung cancer treatment. The drug release profile shows anti-cancer doxorubicin (DOX) loaded S-HAp/PEG/FA/DOX display effective pH-triggered drug release under small pH variations. The extremely high surface area and FA surface functionalization enable a high drug loading capacity and strong anti-cancer killing effects. This is the first demonstration of highly porous sulfate doped HAp nanospheres with FA modification as biodegradable carriers for drug delivery. We believe this work can be extended to other drug carrier designs as well as pH-responsive nanoplatform construction for effective tumor-targeting cancer therapy.