Affiliation:
1. Mechanobiology and Regenerative Medicine Laboratory Bioengineering College Chongqing University 174 Shazheng Street, Shapingba District Chongqing 400044 China
2. State Key Laboratory of New Textile Materials and Advanced Processing Technologies School of Environmental Engineering Wuhan Textile University No. 1 Sunshine Avenue, Jiangxia District Wuhan Hubei Province 430200 China
3. State Key Laboratory of New Textile Materials and Advanced Processing Technologies Wuhan Textile University No. 1 Sunshine Avenue, Jiangxia District Wuhan Hubei Province 430200 China
Abstract
AbstractCurrently, 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.
Funder
National Natural Science Foundation of China
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials