文献类型：期刊文献

英文题名：Mitochondria-Targeted Hydroxyapatite Nanoparticles for Selective Growth Inhibition of Lung Cancer in Vitro and in Vivo

作者：Sun, Yi[1];Chen, Yaying[2];Ma, Xiaoyu[2];Yuan, Yuan[2];Liu, Changsheng[1,2];Kohn, Joachim[3];Qian, Jiangchao[1]

机构：[1]East China Univ Sci & Technol, Minist Educ, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China;[3]Rutgers State Univ, Dept Chem & Chem Biol, New Jersey Ctr Biomat, New Brunswick, NJ 08855 USA

年份：2016

卷号：8

期号：39

起止页码：25680

外文期刊名：ACS APPLIED MATERIALS & INTERFACES

收录：;EI(收录号：20164202901528);WOS:【SCI-EXPANDED(收录号:WOS:000384951800007)】；

语种：英文

外文关键词：hydroxyapatite nanoparticles; lung cancer; mitochondrion-targeted; cytotoxicity; uptake

摘要：Lung cancer is the leading cause of cancer related mortality worldwide. Most patients have metastases at the time of diagnosis, thus demanding development of more effective and specific agents. In this study, the specific anticancer effect of hydroxyapatite nanoparticles (HAPNs) to human lung cancer cells (A549) and the underlying mechanisms were investigated, using normal bronchial epithelial cells (16HBE) as the control. Rod-shaped HAPNs (similar to 10 nm in width and 50 nm in length) were prepared by aqueous precipitation method. Without any further functionalization and drug loading, HAPNs selectively inhibited cancer cell proliferation. Their efficient mitochondrial targeting correlated strongly with decreased mitochondrial membrane potential and induction of mitochondria-dependent apoptosis in A549 cells. Caveolae-mediated endocytosis via lysosome trafficking was observed to be a prominent internalization pathway for HAPNs in both A549 and 16HBE cells. However, more nanoparticles were taken up into A549 cells. HAPNs triggered a sustained elevation of intracellular calcium concentration ([Ca2+](i)) in cancer cells but only a transitory increase in normal control cells. In a nude mouse lung cancer model with xenotransplanted A549 cells, HAPN treatment demonstrated nearly 40% tumor growth inhibition without apparent side effect. These results demonstrated that the enhanced cellular uptake and mitochondrial targeting of HAPNs, together with the prolonged elevation of [Ca2+](i), in A549 cells, could result in the cancer-specific cytotoxicity of HAPNs. Thus, HAPNs might be a promising agent or mitochondria-targeted delivery system for effective lung cancer therapy.