Reversing breast cancer bone metastasis by metal organic framework-capped nanotherapeutics via suppressing osteoclastogenesis.

Abstract

Bone metastasis is the major cause of cancer-related morbidity and mortality. To avoid further osteolysis, current treatment ideas focus on tumor cell and the inhibition of osteoclast. Herein, zeolitic imidazolate framework-8-capped Cu_2-XSe composite nanoplatform (ICG@Cu_2-XSe-ZIF-8) is developed for chemodynamic therapy (CDT) and photothermal therapy (PTT) treatment of malignant breast cancer bone tumors. The rational design of ZIF-8 encapsulation greatly reduces the accumulation of Cu_2-XSe to damage the normal cells. Under acidic microenvironment in tumor, ZIF-8 is cleaved to release Cu_2-XSe, which can subsequently degrade into Cu (+) and Cu (2+) ions to initiate a Fenton-like reaction inducing CDT. Meanwhile, Cu_2-XSe is used to be an effective photothermal transduction agent for exerting the PTT effect. What's more, the selenium element in Cu_2-XSe can regulates selenoprotein to inhibit tumor cells and osteoclasts. Of note, the hyperthermia induced by PTT can further enhance the CDT effect in tumor, achieving a synergistic PTT/CDT effect. Based on these advantages, ICG@Cu_2-XSe-ZIF-8 effectively suppresses the tumor cells in bone tissue, and reduces the erosion of bone tissue via suppressing osteoclastogenesis. In conclusion, this study demonstrates the potential action mechanism of ZIF-8-capped nanomedicine against osteolysis in bone metastasis.