Rhein-PEG-nHA conjugate as a bone targeted drug delivery vehicle for enhanced cancer chemoradiotherapy

Bone-targeted therapies have been the choice of treatments for cancer metastases in bone to minimize skeletal morbidity and preserve patients' quality of life . Rhein is of particular interest due to its high bone affinity. Here we reported a novel Rhein- polyethylene glycol (PEG)-nano hydroxyapatite (nHA) conjugate to deliver doxorubicin (DOX) and Phosphorus-32 ( 32 P) simultaneously for enhanced cancer chemo-radiotherapy. The synthetic Rhein-PEG-nHA conjugates were sphere in shape with an average diameter of ~120 nm . Their morphology, drug release and bone affinity were confirmed in vitro . The release profiles of DOX depend on pH condition , but 32 P exhibited good stability. Rhein-PEG-nHA also showed high bone affinity in vivo , and the tumor volume decreased after the [email protected] and 32 [email protected] treatments. Most importantly, the DOX/ 32 [email protected] showed the strongest inhibition on the growth of bone metastases of breast cancer. We revealed the potential of Rhein-PEG-nHA in combined chemo-radiation treatment for bone metastases of breast cancer.