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Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release
Qiao, Han1; Cui, Zhaowen2; Yang, Shengbing1; Ji, Dingkun3; Wang, Yugang1; Yang, Ying1; Han, Xiuguo1; Fan, Qiming1; Qin, An1; Wang, Tingyu4; He, Xiao-Peng3; Bu, Wenbo2,5; Tang, Tingting1
2017
发表期刊ACS Nano
ISSN19360851
卷号11期号:7页码:7259-7273
摘要The early detection and thus treatment of breast cancer bone metastasis remain a big challenge clinically. As the most abundant cells within bone tissue, osteocytes have been found to manipulate the activity of early cancer bone metastasis by its crosstalk with cancer cells and osteoclasts. However, conventional bone-targeting nanomedicine has limited bone-lesion specificity and ignores the vital role of osteocytes during breast cancer bone metastasis. Also, it lacks detailed insight into the therapeutic mechanisms, which hinders the following translational practice. Previously, we have shown that a combination of zoledronic acid (ZA) and plumbagin (PL) synergistically alleviates cancer-induced bone destruction. Herein, we further develop a pH-responsive bone-targeting drug delivery system, i.e., the ZA-anchored bimodal mesoporous slica covered gadolinium(III) upconversion nanoparticles loaded with PL, to detect and treat bone metastasis sensitively and specifically at an early stage. This multifunctional nanosystem can target osteocytes to release PL as controlled by pH, decreasing osteocytic RANKL expression synergistically through the structural simulation of adenosine phosphate, which competitively inhibits the phosphorylation of osteocytic protein kinase-a, cAMP-response element binding protein, extracellular regulated protein kinase, and c-Jun N-terminal kinase. More importantly, by establishing a breast cancer bone metastasis mice model via intracardiac injection, we show that tumoriogenesis and osteoclastogenesis can both be attenuated significantly. We thereby realize the effective theranostics of tiny bone metastasis in breast cancer bone metastasis. Our work highlights the significance of theranostic nanomedicine and osteocyte-targeting therapy in the treatment of early bone metastasis, which could be applied in achieving efficient theranostic effects for other bone diseases. © 2017 American Chemical Society.
DOI10.1021/acsnano.7b03197
EI入藏号20173103997684
EI主题词Targeted drug delivery
EI分类号461 Bioengineering and Biology - 761 Nanotechnology - 933 Solid State Physics
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.sic.ac.cn/handle/331005/25523
专题中国科学院上海硅酸盐研究所
作者单位1.Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai; 200011, China;
2.State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai; 200050, China;
3.Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai; 200237, China;
4.Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai; 200011, China;
5.Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai; 200062, China
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GB/T 7714
Qiao, Han,Cui, Zhaowen,Yang, Shengbing,et al. Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release[J]. ACS Nano,2017,11(7):7259-7273.
APA Qiao, Han.,Cui, Zhaowen.,Yang, Shengbing.,Ji, Dingkun.,Wang, Yugang.,...&Tang, Tingting.(2017).Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release.ACS Nano,11(7),7259-7273.
MLA Qiao, Han,et al."Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release".ACS Nano 11.7(2017):7259-7273.
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