title: CREKA peptide-conjugated dendrimer nanoparticles for glioblastoma multiforme delivery.
abstract: Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS) tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the glioblastoma parenchyma were crucial challenges in GBM nanomedicine therapy. Nanoparticle diameter can significantly influence the delivery efficiency in tumor tissue. Decreasing nanoparticle size can improve the nanoparticle penetration in tumor tissue but decrease the nanoparticle retention effect. Therefore, small nanoparticles with high retention effect in tumor are urgently needed for effective GBM drug delivery. In present study, a small nanoparticle drug delivery system was developed by conjugating fibrin-binding peptide CREKA to Polyamidoamine (PAMAM) dendrimer, where PEGylated PAMAM is used as drug carrier due to its small size and good penetration in tumor and CREKA is used to target the abundant fibrin in GBM for enhanced retention in tumor. In vitro binding ability tests demonstrated that CREKA can significantly enhanced nanoparticle binding with fibrin. In vivo fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen slices fluorescence imaging further revealed that the CREKA-modified PAMAM achieved higher accumulation and deeper penetration in GBM tissue than unmodified one. These results indicated that the CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for brain tumor therapy.
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Jingjing
authors: J
authors: Zhao
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Bo
authors: B
authors: Zhang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Shun
authors: S
authors: Shen
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Jun
authors: J
authors: Chen
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Qizhi
authors: Q
authors: Zhang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors: Xinguo
authors: X
authors: Jiang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China; Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: zqpang@fudan.edu.cn.
authors: Zhiqing
authors: Z
authors: Pang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D050091:Dendrimers; D009842:Oligopeptides; C104700:PAMAM Starburst; C542438:cysteinyl-arginyl-glutamyl-lysyl-alanyl; D005337:Fibrin
keywords: CREKA peptide; Glioblastoma; Penetration; Polyamidoamine dendrimer; Retention effect