期刊
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 15, 期 4, 页码 482-491出版社
SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2019.05.002
关键词
In situ ApoE-enriched corona; DHA decoration; Nanoparticulate drug delivery system; LDLr-mediated tumor-homing chemotherapy
资金
- Anhui University of Chinese Medicine Foundation [2019zrzd13]
- Key Project of Anhui Province Department of Education [KJ2019A0471]
- Key Project of Liaoning Province Department of Education [2017LZD03]
- National Nature Science Foundation of China [81473164, 81703451, 81873019, 81873351, U1608283]
The therapeutic efficiency of active targeting nanoparticulate drug delivery systems (nano-DDS) is highly compromised by the plasma proteins adsorption on nanoparticles (NPs) surface, which significantly hinders cell membrane receptors to recognize the designed ligands, and provokes the off-target toxicity and rapid clearance of NPs in vivo. Herein, we report a novel dihydroartemisinin (DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E (apoE) on the NPs surface. The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA (PPD) NPs circulation capability in blood, facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention (EPR) effect and low-density lipoprotein receptor (LDLr)-mediated target transport, and ultimately improve the in vivo antitumor activity. Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy. (C) 2019 Published by Elsevier B.V.
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