The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines

doi:10.1021/acs.biomac.8b00083

CORC > 化学研究所 > 中国科学院化学研究所

	The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines
	Lin, Wenhai 1,2; Yin, Lei 3,4; Sun, Tingting 1,2; Wang, Tingting 3,4; Xie, Zhigang 1; Gu, Jingkai 3,4; Jing, Xiabin 1
刊名	BIOMACROMOLECULES
	2018-05-01
卷号	19 期号:5 页码:1625-1634
ISSN号	1525-7797
DOI	10.1021/acs.biomac.8b00083
英文摘要	Fundamental studies on the cellular uptake and drug release of PEGylated nanomedicines are beneficial to understand their fate in vivo and construct ideal nanoparticle formulations. In this work, the detailed metabolic process of PEGylated doxorubicin (Dox) nanomedicines were investigated via confocal laser scanning microscopy (CLSM), flow cytometry (FCM), cytotoxicity test, fluorescence imaging in vivo (FLIV) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Among them, only LC-MS/MS could accurately determine the content of PEGylated Dox and Dox in vitro and in vivo. To the best of our knowledge, this was the first time the PEGylated Dox and released Dox were simultaneously quantified. The interplay of molecular structures, cellular uptake, drug release, and antitumor effect was well characterized. PEG with high molecular weight impeded the cellular uptake of nanoparticles, and the acid-labile hydrazone bond between Dox and PEG promoted Dox release significantly. Cellular uptake and drug release play decisive roles in cytotoxicity and antitumor effect, as evidenced by LC-MS/MS. We emphasized that LC-MS/ MS would be a practicable method to quantify PEGylated drugs without complex tags, which could be more in-depth to understand the interaction between PEGylated nanomedicines and their antitumor efficacy.
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000432476800025
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/42741]
专题	中国科学院化学研究所
通讯作者	Xie, Zhigang; Gu, Jingkai
作者单位	1.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, 5625 Renmin St, Changchun 130022, Jilin, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Jilin Univ, Coll Life Sci, Res Ctr Drug Metab, Changchun 130012, Jilin, Peoples R China 4.Jilin Univ, Hosp 1, Res Inst Translat Med, Clin Pharmacol Ctr, Dongminzhu St, Changchun 130061, Jilin, Peoples R China
推荐引用方式 GB/T 7714	Lin, Wenhai,Yin, Lei,Sun, Tingting,et al. The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines[J]. BIOMACROMOLECULES,2018,19(5):1625-1634.
APA	Lin, Wenhai.,Yin, Lei.,Sun, Tingting.,Wang, Tingting.,Xie, Zhigang.,...&Jing, Xiabin.(2018).The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines.BIOMACROMOLECULES,19(5),1625-1634.
MLA	Lin, Wenhai,et al."The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines".BIOMACROMOLECULES 19.5(2018):1625-1634.