Ph-sensitive polymeric nanoparticles with gold(i) compound payloads synergistically induce cancer cell death through modulation of autophagy
文献类型：期刊论文
| 作者 | Lin, Yao-Xin1,2; Gao, Yu-Juan1; Wang, Yi1,2; Qiao, Zen-Ying1; Fan, Gang1; Qiao, Sheng-Lin1,2; Zhang, Ruo-Xin1; Wang, Lei1; Wang, Hao1 |
| 刊名 | Molecular pharmaceutics
 |
| 出版日期 | 2015-08-01 |
| 卷号 | 12期号:8页码:2869-2878 |
| 关键词 | Autophagy Ros Ph-sensitive Polymer Nanoparticles Cancer |
| ISSN号 | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.5b00060 |
| 通讯作者 | Wang, hao(wanghao@nanoctr.cn) |
| 英文摘要 | Various nanomaterials have been demonstrated as autophagy inducers owing to their endocytosis cell uptake pathway and impairment of lysosomes. ph-dependent nanomaterials as drug delivery systems that are capable of dissociating in weakly acidic lysosomal environment (ph 45) and consequently releasing the payloads into the cytoplasm have been paid extensive attention, but their autophagy-modulating effects are less reported so far. in this study, we report ph-sensitive micelle-like nanoparticles (nps) that self-assembled from poly(beta-amino ester)s to induce cell autophagy. by encapsulation of gold(i) compounds (au(i)) into hydrophobic domains of nps, the resultant au(i)-loaded nps (au(i)subset of nps) shows synergistic cancer cell killing performance. the au(i)subset of nps enter cells through endocytosis pathway and accumulate into acidic lysosomes. subsequently, the protonation of tertiary amines of poly(beta-amino ester)s triggers the dissociation of micelles, damages the lysosomes, and blocks formation of autolysosomes from fusion of lysosomes with autophagosomes. in addition, au(i) preferentially inhibits thioredoxin reductase (trxr) in mcf-7 human breast cancer cells that directly links to up-regulate reactive oxygen species (ros) and consequently induce autophagy and apoptosis. the blockade of autophagy leads to excessive depletion of cellular organelles and essential proteins and ultimately results in cell death. therefore, ph-sensitive polymeric nanoparticles with gold(i) compound payloads can synergistically induce cancer cell death through regulation of autophagy. identification of the ph-sensitive nanomaterials for synergistically inducing cell death through regulation autophagy may open a new avenue for cancer therapy. |
| WOS关键词 | INTRACELLULAR DRUG-DELIVERY ; ORTHO ESTER GROUPS ; THERAPEUTIC APPLICATIONS ; POLY(BETA-AMINO ESTER)S ; OLIGO(ETHYLENE GLYCOL) ; THIOREDOXIN REDUCTASE ; TRIGGERED RELEASE ; ANTICANCER DRUGS ; CYSTIC-FIBROSIS ; QUANTUM DOTS |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| WOS类目 | Medicine, Research & Experimental ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000359096100029 |
| 出版者 | AMER CHEMICAL SOC |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2176413 |
| 专题 | 高能物理研究所 |
| 通讯作者 | Wang, Hao |
| 作者单位 | 1.Chinese Acad Sci, Key Lab Biol Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol NCNST, Beijing, Peoples R China 2.Univ Chinese Acad Sci UCAS, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Yao-Xin,Gao, Yu-Juan,Wang, Yi,et al. Ph-sensitive polymeric nanoparticles with gold(i) compound payloads synergistically induce cancer cell death through modulation of autophagy[J]. Molecular pharmaceutics,2015,12(8):2869-2878. |
| APA | Lin, Yao-Xin.,Gao, Yu-Juan.,Wang, Yi.,Qiao, Zen-Ying.,Fan, Gang.,...&Wang, Hao.(2015).Ph-sensitive polymeric nanoparticles with gold(i) compound payloads synergistically induce cancer cell death through modulation of autophagy.Molecular pharmaceutics,12(8),2869-2878. |
| MLA | Lin, Yao-Xin,et al."Ph-sensitive polymeric nanoparticles with gold(i) compound payloads synergistically induce cancer cell death through modulation of autophagy".Molecular pharmaceutics 12.8(2015):2869-2878. |
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来源：高能物理研究所
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