title: Increased Active Tumor Targeting by An αvβ3-Targeting and Cell-Penetrating Bifunctional Peptide-Mediated Dendrimer-Based Conjugate.
abstract: A bifunctional RGDTAT peptide-modified PEG-PAMAM dendrimer conjugate RGDTAT-PEG-PAMAM (RTPP) was established for the targeted treatment of αvβ3-overexpressing tumor cells.
  
  
  
  The RGDTAT peptide was synthesized and attached to PAMAM using PEG to construct the RTPP conjugate. The methotrexate (MTX) encapsulated RTPPM complex was prepared and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and in vitro release. The targeting ability was then studied in cells and tumor-bearing nude mice using fluorescence microscopy, confocal fluorescence microscopy, flow cytometry, and in vivo imaging. The cytotoxicity and pharmacokinetics of the RTPPM complex was also evaluated in cells and rats.
  
  
  
  The successful synthesis of the RTPP conjugate was confirmed by1H-NMR. DLS and TEM measurements revealed that the size was 37 nm and the complex had a spherical shape. RTPP and RTPPM were taken up by αvβ3-overexpressing cells more efficiently than by αvβ3-lowexpressing cells. The RTPP conjugate localized to the cell nucleus and accumulated in the tumor more efficiently than did the conjugates without RGDTAT. The pharmacokinetic study of the RTPPM complex showed sustained drug release.
  
  
  
  The bifunctional peptide-mediated dendrimer-based RTPP conjugate can serve as a promising nanocarrier for targeted drug delivery to improve anti-tumor activity.
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.|School of Chinese Materia Medica, Beijing University of Chinese Medicine, NO. 6 Wangjing Road, 100102, Beijing, China.
authors.forename: Pengkai
authors.initials: P
authors.lastname: Ma
authors.affiliation: Yantai Yuhuangding hospital, No. 20, Yuhuangding East Road, Yantai, 264000, Shandong, China.
authors.forename: Huajun
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Mu
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Chu
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ni
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Xing
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, People's Republic of China. sunkx@ytu.edu.cn.
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008727:Methotrexate / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; C522249:PEG-PAMAM; D011092:Polyethylene Glycols; D008727:Methotrexate
keywords: PAMAM; RGD peptide; active tumor targeting; cell-penetrating peptide; chemotherapeutic drug; methotrexate