title: Efficient cytosolic delivery mediated by  polymersomes facilely prepared from a  degradable, amphiphilic, and amphoteric  copolymer.
abstract: To solve problems in polymersome preparation caused by liposolubility of copolymers and to improve the cytosolic delivery efficiency of polymersomes to drugs, a lipopolysaccharide-amine (LPSA) copolymer with amphotericity and amphiphilicity is developed. LPSA contains two hydrophilic oppositely charged blocks (anionic oxidized alginate (OA), cationic polyethyleneimine (PEI 1.8 k)) and one hydrophobic block (cholesteryl), where OA is the backbone and cholesteryl-grafted PEI is the side chain. The two hydrophilic blocks first guarantee that LPSA will dissolve in water, and then help polymersome formation via electrostatic interactions to generate water insoluble interpolyelectrolyte complexes, which supplement the hydrophobic part to reach the right hydrophilicity/hydrophobicity ratio, and thus realize a one-step self-assembly of polymersomes in water. Our results show LPSA nanopolymersomes (LNPs) have low cytotoxicity and degradability, and an excellent ability to enter cells. TEM observation demonstrates that LNPs are entrapped in endosomes after endocytosis, and are then released to cytosols because of their strong endosomal escape capacity. As an example of cytosolic delivery to bioactive molecules, pDNA is delivered in mesenchymal stem cells, and more than 95% of cells express a large target protein, indicating that LNPs have high cytosolic delivery efficiency. Our study provides a novel, easy, and universal method to design copolymers for the preparation of polymersomes as efficient cytosolic delivery nanocarriers.
authors.affiliation: Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangdong 510080, People’s Republic of China.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Teng
authors.forename: Longshan
authors.initials: L
authors.lastname: Liu
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Qinmei
authors.initials: Q
authors.lastname: Wang
authors.forename: Yugang
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D016503:Drug Delivery Systems; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles / Q000648:ultrastructure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012996:Solutions; D013055:Spectrophotometry, Infrared; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection; D014867:Water
chemical_list: D000588:Amines; D008070:Lipopolysaccharides; D011108:Polymers; D012996:Solutions; D013501:Surface-Active Agents; C485184:enhanced green fluorescent protein; D014867:Water; D049452:Green Fluorescent Proteins