title: Liposomes co-modified with cholesterol anchored cleavable PEG and octaarginines for tumor targeted drug delivery.
abstract: Tumor targeted drug delivery system with high efficiency of tumor accumulation, cell internalization and endosomal escape was considered ideal for cancer therapy. Herein, a cleavable polyethylene glycol (PEG) and octaarginines (R8) co-modified liposome (CL-R8-LP) was developed, in which the cholesterol was used as an alternative anchor to the commonest phospholipids for the diversified development of surface modification. The in vitro hemolysis assay and bio-distribution study demonstrated that CL-R8-LP improved biocompatibility and tumor accumulation compared with the single R8 modified liposomes (R8-LP), since the strong positive charges, toxicity and non-specificity of R8 were efficiently shielded by the outer cleavable PEG. And the cellular uptake, cytotoxicity and apoptosis of CL-R8-LP on C26 cells were much stronger than that of control liposomes in which R8 was not included or exposed. In addition, it was confirmed that CL-R8-LP entered cells via clathrin-mediated endocytosis and the macropinocytosis, and followed by a more efficient endosomal escape compared with R8-LP due to the topology change of R8. The enhanced in vivo delivery efficiency and anti-tumor efficacy were validated in C26 bearing mice. In conclusion, the results demonstrated that CL-R8-LP was a promising vehicle for enhancing the chemotherapy of solid cancers.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu, Sichuan , P.R. China and.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Han
authors.initials: H
authors.lastname: Fu
authors.forename: Qifang
authors.initials: Q
authors.lastname: Kuang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yayuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Ran
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry* / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008081:Liposomes; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011817:Rabbits; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; C448619:octaarginine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol