Hierarchically Released Liquid Metal Nanoparticles for Mild Photothermal Therapy/Chemotherapy of Breast Cancer Bone Metastases via Remodeling Tumor Stromal Microenvironment

Abstract

Currently, the treatment strategy for bone metastasis is mainly to inhibit the growth of tumor cells and the activity of osteoclasts, while ignoring the influence of the tumor stromal microenvironment (TSM) on the progression of bone metastasis. Herein, a dual‐target liquid metal (LM)‐based drug delivery system (DDS) with favorable photothermal performance is designed to spatially program the delivery of multiple therapeutic agents to enhance the treatment of bone metastasis through TSM remodeling. Briefly, mesoporous silicon‐coated LM is integrated into zeolitic imidazolate framework‐8 (ZIF‐8) with both bone‐seeking and tumor‐targeting capacities. Curcumin (Cur), a tumor microenvironment modulator, is encapsulated into ZIF‐8, and doxorubicin (DOX) is enclosed inside mesoporous silicon. Specific accumulation of the LM‐based DDS in bone metastases first relieves the tumor stroma by releasing Cur in response to the acidic tumor microenvironment and then releases DOX deep into the tumor under near‐infrared light irradiation. The combined strategy of the LM‐based DDS and mild photothermal therapy has been shown to effectively restrain cross‐talk between osteoclasts and tumor cells by inhibiting the secretion of transforming growth factor‐β, degrading extracellular matrix components, and increasing infiltration of CD4+ and CD8+ T cells, which provides a promising strategy for the treatment of bone metastases.

Unravelling the Metastatic Niche in Breast Cancer Patients with Bone Metastasis through Single-cell RNA Sequencing

“…The main treatment strategy for BoM is to inhibit the growth of tumor cells while ignoring the in uence of the tumor stromal microenvironment on the progression of BoM 4 . The intricate landscape of the tumor microenvironment (TME) is composed of diverse noncellular factors and a myriad of cell types, including cancer-associated broblasts (CAFs), immune cells, endothelial cells, pericytes, and adipocytes.…”

Unraveling the Metastatic Niche in Breast Cancer Bone Metastasis through Single-Cell RNA Sequencing

“…Main treatment strategy for BoM is to inhibit the growth of tumor cells, while ignoring the in uence of the tumor stromal microenvironment (TSM) on the progression of BoM 4 . The intricate landscape of the tumor microenvironment (TME) is composed of diverse non-cellular factors and a myriad of cell types, including cancer-associated broblasts (CAFs), immune cells, endothelial cells, pericytes, and adipocytes.…”