title: Liposome-Based Systemic Glioma-Targeted Drug Delivery Enabled by All-d Peptides.
abstract: As the most aggressive brain tumor, chemotherapy of malignant glioma remains to be extremely challenging in clinic. The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) are physiological and pathological barriers preventing therapeutic drugs from reaching the glioma region. In addition, vasculogenic mimicry (VM) formed by invasive glioma cells instead of endothelial cells and angiogenesis are very common in glioma, leading to the poor prognosis and recurrence of glioma. An ideal drug delivery system for glioma chemotherapy needs to traverse the BBB and BBTB and then target VM, angiogenesis, and glioma cells. Herein we developed a liposome-based drug delivery system with the modification of proteolytically stable d-peptide ligands (dCDX/dA7R-LS).dCDX is a d-peptide ligand of nicotine acetylcholine receptors (nAChRs) capable of circumventing the BBB, anddA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed on angiogenesis, VM, and glioma, presenting excellent glioma-homing property.dCDX/dA7R-LS could efficiently internalize into the brain capillary endothelial cells, glioma cells, tumor neovascular endothelial cells, and tumor spheroids and cross the in vitro BBB and BBTB models. Ex vivo imaging and in vivo immunofluorescence assays confirmed the superiority ofdCDX/dA7R-LS in targeting intracranial glioma in comparison to plain liposomes or liposomes modified with an individual d-peptide ligand (eitherdCDX ordA7R). When loaded with doxorubicin,dCDX/dA7R-LS achieved the best antiglioma, antiangiogenesis, and anti-VM effects among all tested formulations. These results suggested that systemic glioma-targeted drug delivery enabled by all-d peptide ligands was promising for the antiglioma therapy.
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Man
authors: M
authors: Ying
authors: 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: Changyou
authors: C
authors: Zhan
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Songli
authors: S
authors: Wang
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Bingxin
authors: B
authors: Yao
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Xuefeng
authors: X
authors: Hu
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Xianfei
authors: X
authors: Song
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Mingfei
authors: M
authors: Zhang
authors: 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: Xiaoli
authors: X
authors: Wei
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
authors: Yan
authors: Y
authors: Xiong
authors: 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.|State Key Laboratory of Molecular Engineering of Polymers, Fudan University , Shanghai 200433, China.
authors: Weiyue
authors: W
authors: Lu
mesh_terms: D001812:Blood-Brain Barrier; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005910:Glioma; D006801:Humans; D008081:Liposomes; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A
chemical_list: D008081:Liposomes; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A
keywords: dA7R; dCDX; glioma; liposomes; systemic targeted drug delivery