title: Reduction-Degradable Polymeric Micelles Decorated with PArg for Improving Anticancer Drug Delivery Efficacy.
abstract: In this study, five kinds of reduction-degradable polyamide amine-g-polyethylene glycol/polyarginine (PAA-g-PEG/PArg) micelles with different proportions of hydrophilic and hydrophobic segments were synthesized as novel drug delivery vehicles. Polyarginine not only acted as a hydrophilic segment but also possessed a cell-penetrating function to carry out a rapid transduction into target cells. Polyamide amine-g-polyethylene glycol (PAA-g-PEG) was prepared for comparison. The characterization and antitumor effect of the DOX-incorporated PAA-g-PEG/PArg cationic polymeric micelles were investigated in vitro and in vivo. The cytotoxicity experiments demonstrated that the PAA-g-PEG/PArg micelles have good biocompatibility. Compared with DOX-incorporated PAA-g-PEG micelles, the DOX-incorporated PAA-g-PEG/PArg micelles were more efficiently internalized into human hepatocellular carcinoma (HepG2) cells and more rapidly released DOX into the cytoplasm to inhibit cell proliferation. In the 4T1-bearing nude mouse tumor models, the DOX-incorporated PAA-g-PEG/PArg micelles could efficiently accumulate in the tumor site and had a longer accumulation time and more significant aggregation concentration than those of PAA-g-PEG micelles. Meanwhile, it excellently inhibited the solid tumor growth and extended the survival period of the tumor-bearing Balb/c mice. These results could be attributed to their appropriate nanosize and the cell-penetrating peculiarity of polyarginine as a surface layer. The PAA-g-PEG/PArg polymeric micelles as a safe and high efficiency drug delivery system were expected to be a promising delivery carrier that targeted hydrophobic chemotherapy drugs to tumors and significantly enhanced antitumor effects.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Yani
authors.initials: Y
authors.lastname: Cui
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Sui
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: He
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fan
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University , 29 Wangjiang Road, Chengdu 610064, China.
authors.forename: Xingdong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D061848:Optical Imaging; D009928:Organ Specificity / Q000187:drug effects; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D010455:Peptides; D011108:Polymers; C015462:polyarginine; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: cell-penetrating; doxorubicin; micelles; polyarginine; reduction-degradable