title: Design strategy of cell-penetrating copolymers for high efficient drug delivery.
abstract: Finding a highly effective drug delivery carrier with low cytotoxicity is essential for disease therapy. In this work, we design a cell-penetrating copolymer (CPC) carrier, in which the inspiration comes from cell-penetrating peptides that have both hydrophilic and hydrophobic residues and are capable of penetrating membranes without inducing membrane disruption. Further dissipative particle dynamics simulations indicate that the CPCs also have an effective penetration capacity. Importantly, we found that the penetration mechanism of the CPC is in a zipper way, i.e. the adjacent hydrophobic segments of the CPC could cross the membrane in a cooperative way. Moreover, we determine the optimal parameters for the CPC crossing lipid membrane, i.e. the hydrophobic segment length of the CPC is close to the membrane thickness, and the CPC has more segment number. Finally, by grafting the CPC with the optimal structure on the hydrophilic drug, we found that the CPCs can definitely help the hydrophilic drug penetrate the lipid membrane effectively, which is an excellent prototype of drug delivery carriers. It is expected that this work can provide the fundamental for further design of drug delivery carriers.
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China.
authors.forename: Diwen
authors.initials: D
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: zhangxr@mail.buct.edu.cn.
authors.forename: Xianren
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: caodp@mail.buct.edu.cn.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Cao
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D008051:Lipid Bilayers; D011108:Polymers
keywords: Cell-penetrating copolymer; Dissipative particle dynamics simulation; Drug delivery carriers; Penetration mechanism