title: Glioma therapy using tumor homing and penetrating peptide-functionalized PEG-PLA nanoparticles loaded with paclitaxel.
abstract: By taking advantage of the excessively upregulated expression of neuropilin (NRP) on the surface of both glioma cells and endothelial cells of angiogenic blood vessels, the ligand of NRP with high affinity - tLyp-1 peptide, which also contains a CendR motif ((R/K)XX(R/K)), was functionalized to the surface of PEG-PLA nanoparticles (tLyp-1-NP) to mediate its tumor homing, vascular extravasation and deep penetration into the glioma parenchyma. The tLyp-1-NP was prepared via a maleimide-thiol coupling reaction with uniformly spherical shape under TEM and particle size of 111.30 ± 15.64 nm. tLyp-1-NP exhibited enhanced cellular uptake in both human umbilical vein endothelial cells and Rat C6 glioma cells, increased cytotoxicity of the loaded PTX, and improved penetration and growth inhibition in avascular C6 glioma spheroids. Selective accumulation and deep penetration of tLyp-1-NP at the glioma site was confirmed by in vivo imaging and glioma distribution analysis. The longest survival was achieved by those mice bearing intracranial C6 glioma treated with PTX-loaded tLyp-1-NP. The findings here strongly indicate that tLyp-1 peptide-functionalized nanoparticulate DDS could significantly improve the efficacy of paclitaxel glioma therapy.
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, PR China.
authors: Quanyin
authors: Q
authors: Hu
authors: Xiaoling
authors: X
authors: Gao
authors: Guangzhi
authors: G
authors: Gu
authors: Ting
authors: T
authors: Kang
authors: Yifan
authors: Y
authors: Tu
authors: Zhongyang
authors: Z
authors: Liu
authors: Qingxiang
authors: Q
authors: Song
authors: Lei
authors: L
authors: Yao
authors: Zhiqing
authors: Z
authors: Pang
authors: Xinguo
authors: X
authors: Jiang
authors: Hongzhuan
authors: H
authors: Chen
authors: Jun
authors: J
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D003374:Coumarins / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D019265:Spectroscopy, Near-Infrared; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D057846:Cell-Penetrating Peptides; D003374:Coumarins; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; C030123:coumarin; D017239:Paclitaxel