title: "Sheddable" PEG-lipid to balance the contradiction of PEGylation between long circulation and poor uptake.
abstract: PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a "sheddable" PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic microenvironment, the PEG chains detached from the surfaces of the micelles while the degree of linker cleavage could not cause a significant particle size change, which facilitated the carrier binding to tumor cells and improved the cellular uptake. Subsequently, the "sheddable" PEG-lipid micelles easily internalized into cells and the increased acidity in the lysosomes further promoted drug release. Thus, this "sheddable" PEG-lipid nanocarrier could be a good candidate for effective intracellular drug delivery in cancer chemotherapy.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Caiyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn and Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China.
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Deng
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Li
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Leihou
authors.initials: L
authors.lastname: Shao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China. liangxj@nanoctr.cn wuy@nanoctr.cn.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang