文献类型：期刊文献

英文题名：Targeting Osteocytes to Attenuate Early Breast Cancer Bone Metastasis by Theranostic Upconversion Nanoparticles with Responsive Plumbagin Release

作者：Qiao, Han[1];Cui, Zhaowen[2];Yang, Shengbing[1];Ji, Dingkun[3,4];Wang, Yugang[1];Yang, Ying[1];Han, Xiuguo[1];Fan, Qiming[1];Qin, An[1];Wang, Tingyu[5];He, Xiao-Peng[3,4];Bu, Wenbo[2,6];Tang, Tingting[1]

机构：[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Orthopaed Implants, Dept Orthopaed Surg,Shanghai Peoples Hosp 9, Shanghai 200011, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China;[3]East China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Inst Fine Chem, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[5]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Pharm, Shanghai 200011, Peoples R China;[6]East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, Shanghai 200062, Peoples R China

年份：2017

卷号：11

期号：7

起止页码：7259

外文期刊名：ACS NANO

收录：;EI(收录号：20173103997684);WOS:【SCI-EXPANDED(收录号:WOS:000406649700075)】；

基金：This work was funded by the National Key R&D Plan (2016YFC1102100), National Natural Science Foundation of China (81672205), and the Innovation Program for Ph.D. students in Shanghai Jiaotong University School of Medicine (BXJ201729). We thank Prof. Lynda Bonewald (University of Missouri, USA) and Prof. Jiake Xu (University of Western Australia, Australia) for their kindness in providing MLOY-4 and MDA-MB-231SArfp cells.

语种：英文

外文关键词：upconversion nanoparticle; breast cancer bone metasatasis; theranostic; osteocyte-targeting; ATP competitiveness; plumbagin; zoledronic acid

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.