Bone-Targeted Nanoplatform Combining Zoledronate and Photothermal Therapy To Treat Breast Cancer Bone Metastasis.

Abstract

Bone metastasis, a clinical complication of patients with advanced breast cancer, seriously reduces the quality of life. To avoid destruction of the bone matrix, current treatments focus on inhibiting the cancer cell growth and the osteoclast activity through combination therapy. Therefore, it could be beneficial to develop a bone-targeted drug delivery system to treat bone metastasis. Here, a bone-targeted nanoplatform was developed using gold nanorods enclosed inside mesoporous silica nanoparticles (Au@MSNs) which were then conjugated with zoledronic acid (ZOL). The nanoparticles (Au@MSNs-ZOL) not only showed bone-targeting ability <i>in vivo</i> but also inhibited the formation of osteoclast-like cells and promoted osteoblast differentiation <i>in vitro</i>. The combination of Au@MSNs-ZOL and photothermal therapy (PTT), triggered by near-infrared irradiation, inhibited tumor growth both <i>in vitro</i> and <i>in vivo</i> and relieved pain and bone resorption <i>in vivo</i> by inducing apoptosis in cancer cells and improving the bone microenvironment. This single nanoplatform combines ZOL and PTT to provide an exciting strategy for treating breast cancer bone metastasis.