期刊
SCIENCE CHINA-MATERIALS
卷 64, 期 2, 页码 474-487出版社
SCIENCE PRESS
DOI: 10.1007/s40843-020-1405-8
关键词
targeted nanoparticles; cancer therapy; multifunctional nanoparticles; drug delivery; bone targeting
资金
- National Natural Science Foundation of China [21725402, 31871010, 81971735, 81871470, 81901867]
- Shanghai Municipal Science and Technology Commission [17XD1401600]
- Fok Ying Tong Education Foundation [151036]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06C322]
The study demonstrated that polyethylene glycol-conjugated alendronate-functionalized and chloroquine-loaded polydopamine nanoparticles efficiently inhibited tumor growth and osteolysis by breaking the vicious cycle between tumor cell proliferation and bone resorption, highlighting the potential of autophagy inhibition-associated photothermal therapy as a promising strategy for treating malignant bone tumors.
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 tumorsviabreaking the vicious cycle. The nanoparticles were efficiently accumulated to the bone tissues, especially the osteolytic lesions around tumors. CQ released from PPA/CQ inhibited osteoclastogenesisviapreventing 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, thein vivoexperiment 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.
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