Bisphosphonate-functionalized coordination polymer nanoparticles for the treatment of bone metastatic breast cancer

Bone is the most common organ affected by metastatic breast cancer . Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In this study, a polyethylene glycol (PEG) coated nanoparticles (NPs) made of a Zn 2   + coordination polymer was linked with a bone seeking moiety, alendronate (ALN), to deliver cisplatin prodrug (DSP) to the bone. The particle sizes of this novel system, [email protected] NPs, were regulated by adjusting the volume ratio of water phase to oil phase in microemulsion . It was small enough (about 55   nm) to extravasate through the clefts (80   nm) of the bone's sinusoidal capillaries and localize into metastatic bones. [email protected] NPs showed much higher affinity for hydroxyapatite in vitro and bone in vivo than non-targeted [email protected] NPs and cisplatin. In addition, the in vivo biodistribution studies demonstrated that about 4-fold of platinum was delivered to the bone metastatic lesions than that in healthy bones by [email protected] NPs intravenously. Finally, [email protected] NPs not only inhibited the tumor growth efficiently but also reduced the osteocalastic bone destruction. Besides, [email protected] NPs showed significantly reduced toxicity of cisplatin. These results indicate that the [email protected] NPs have a great potential in enhancing chemotherapeutic efficacy for the treatment of bone metastatic breast cancer.