title: Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB.
abstract: Chemotherapy outcomes for the treatment of glioma remain unsatisfied due to the inefficient drug transport across BBB/BBTB and poor drug accumulation in the tumor site. Nanocarriers functionalized with different targeting ligands are considered as one of the most promising alternatives. However, few studies were reported to compare the targeting efficiency of the ligands and develop nanoparticles to realize BBB/BBTB crossing and brain tumor targeting simultaneously. In this study, six peptide-based ligands (Angiopep-2, T7, Peptide-22, c(RGDfK), D-SP5 and Pep-1), widely used for brain delivery, were selected to decorate liposomes, respectively, so as to compare their targeting ability to BBB or BBTB. Based on the in vitro cellular uptake results on BCECs and HUVECs, Peptide-22 and c(RGDfK) were picked to construct a BBB/BBTB dual-crossing, glioma-targeting liposomal drug delivery system c(RGDfK)/Pep-22-DOX-LP. In vitro cellular uptake demonstrated that the synergetic effect of c(RGDfK) and Peptide-22 could significantly increase the internalization of liposomes on U87 cells. In vivo imaging further verified that c(RGDfK)/Pep-22-LP exhibited higher brain tumor distribution than single ligand modified liposomes. The median survival time of glioma-bearing mice treated with c(RGDfK)/Pep-22-DOX-LP (39.5 days) was significantly prolonged than those treated with free doxorubicin or other controls. In conclusion, the c(RGDfK) and Peptide-22 dual-modified liposome was constructed based on the targeting ability screening of various ligands. The system could effectively overcome BBB/BBTB barriers, target to tumor cells and inhibit the growth of glioma, which proved its potential for improving the efficacy of chemotherapeutics for glioma therapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Cuitian
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Ziqing
authors.identifier: http://orcid.org/0000-0002-2323-7137
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Ruixiang
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Liang
authors.affiliation: Shanghai Xuhui Central Hospital , Shanghai 200031, People's Republic of China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai 201203, People's Republic of China.
authors.forename: Jianxin
authors.identifier: http://orcid.org/0000-0003-0879-5883
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005910:Glioma; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides; D010456:Peptides, Cyclic
chemical_list: D008081:Liposomes; D010455:Peptides; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide
keywords: Peptide-22; blood−brain barrier; blood−brain tumor barrier; c(RGDfK); glioma; liposome