title: Tandem Peptide Based on Structural Modification of Poly-Arginine for Enhancing Tumor Targeting Efficiency and Therapeutic Effect.
abstract: The nonselectivity of cell penetrating peptides had greatly limited the application in systemic administration. By conjugating a dGR motif to the C-terminal of octa-arginine, the formed tandem peptide R8-dGR had been proved to specifically recognize both integrin αvβ3and neuropilin-1 receptors. However, the positive charge of poly-arginine would still inevitably lead to rapid clearance in the circulation system. Therefore, in this study, we tried to reduce the positive charge of poly-arginine by decreasing the number of arginine, to thus achieve improved tumor targeting efficiency. We had designed several different Rx-dGR peptides (x = 4, 6, and 8) modified liposomes and investigated their tumor targeting and penetrating properties both in vitro and in vivo. Among all the liposomes, R6-dGR modified liposomes exhibited a long circulation time similar to that of PEGylated liposomes while they retained strong penetrating ability into both tumor cells and tumor tissues, and thus had displayed the most superior tumor targeting efficiency. Then, paclitaxel and indocyanine green coloaded liposomes were prepared, and R6-dGR modified coloaded liposomes also exhibited enhanced antitumor effect on C6 xenograft tumor bearing mice. Therefore, we suggest R6-dGR as a potential tumor targeting ligand with both strong penetrating ability and improved pharmacokinetic behavior, which could be further used for efficient antitumor therapy.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.|Haisco Pharmaceutical Group Co., Ltd. , Baili road No.136, Cross-Straits IT Industry Development Zone, Wenjiang, Chengdu 611130, China.
authors.forename: Yayuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Zhengze
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Tai
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Yang
authors.identifier: http://orcid.org/0000-0002-7911-9551
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Kairong
authors.initials: K
authors.lastname: Shi
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Zhirong
authors.identifier: http://orcid.org/0000-0001-9118-5394
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University , No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
authors.forename: Qin
authors.identifier: http://orcid.org/0000-0002-2762-2235
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D001120:Arginine; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides; D016503:Drug Delivery Systems; D008081:Liposomes; D051379:Mice; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols
chemical_list: D057846:Cell-Penetrating Peptides; D008081:Liposomes; D009842:Oligopeptides; D010455:Peptides; C015462:polyarginine; D011092:Polyethylene Glycols; D001120:Arginine
keywords: cell penetrating peptide; combination therapy; photothermal therapy; poly-arginine; tandem peptide