Breaking the vicious cycle between tumor cell proliferation and bone resorption by chloroquine-loaded and bone-targeted polydopamine nanoparticles

The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone tumors. Here, we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine (CQ)-loaded polydopamine nanoparticles (PPA/CQ) for efficient treatment of bone tumors via breaking the vicious cycle. The nanoparticles were efficiently accumulated to the bone tissues, especially the osteolytic lesions around tumors. CQ released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor (TNF) receptor-associated receptor 3 to attenuate the osteolysis in bone tumors. On the other hand, CQ blocked the autophagy in cancer cells, resulting in improved photothermal killing of cancer cells. Finally, the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and osteolysis. This work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors.