title: Stabilized Heptapeptide A7R for Enhanced Multifunctional Liposome-Based Tumor-Targeted Drug Delivery.
abstract: (L)A7R (ATWLPPR) is a heptapeptide with high binding affinity in vitro to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed on glioma, glioma vasculogenic mimicry and neovasculature. However, its tumor targeting efficacy is significantly reduced in vivo due to proteolysis in blood circulation. To improve the in vivo stability and targeting efficacy, the retro inverso isomer of (L)A7R ((D)A7R) was developed for glioma-targeted drug delivery. (D)A7R was expected to have a similar binding affinity to its receptors in vitro (VEGFR2 and NRP-1), which was experimentally confirmed. In vivo, (D)A7R-modified liposomes achieved improved glioma-targeted efficiency than did (L)A7R-modified liposomes. After loading a chemotherapeutic agent (doxorubicin), (D)A7R-modified liposomes significantly inhibited subcutaneous model tumor in comparison to free doxorubicin, plain liposomes and (L)A7R-modified liposomes. In summary, the present study presented the potential of a proteolytically stable d-peptide ligand for in vivo tumor-targeted drug delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.
authors.forename: Man
authors.initials: M
authors.lastname: Ying
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.|State Key Laboratory of Molecular Engineering of Polymers, Fudan University , Shanghai 200433, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of chemistry and molecular engineering, East China Normal University , Shanghai 200062, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.|State Key Laboratory of Medical Neurobiology, The Collaborative Innovation Center for Brain Science, Fudan University , Shanghai 200032, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.|Department of Pharmacology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.
authors.forename: Bingxin
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education , Shanghai 201203, China.|State Key Laboratory of Molecular Engineering of Polymers, Fudan University , Shanghai 200433, China.|State Key Laboratory of Medical Neurobiology, The Collaborative Innovation Center for Brain Science, Fudan University , Shanghai 200032, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000503:physiopathology; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D004317:Doxorubicin
keywords: DA7R; liposomes; stability; targeted drug delivery; tumor