title: A 5-fluorouracil-loaded pH-responsive dendrimer nanocarrier for tumor targeting.
abstract: A novel long-circulating and pH-responsive dendrimer nanocarrier was prepared for delivering 5-fluorouracil (5-FU) to tumors through the targeting of nanoparticles to the low pH environment of tumors. The nanocarrier, poly(2-(N,N-diethylamino)ethyl methacrylate) with methoxy-poly(ethylene glycol)-poly(amidoamine) (PPD), had a core-shell structure with 4.0 G poly(amidoamine) (PAMAM) as the core and parallel poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEA) chains and methoxy-poly(ethylene glycol) (mPEG) chains as the shell. The PDEA chain was pH-responsive, and the PEG chains led to long circulation in blood vessels to achieve tumor targeting. The sizes, drug encapsulation and release of PPD nanocarriers showed high pH-dependency due to the PDEA chains, as they were hydrophilic at pH 6.5 and hydrophobic at pH 7.4. The encapsulation efficiency of 5-FU in PPD nanocarriers was as high as 92.5% through the pH transition. The release of 5-FU from PPD nanocarriers was much faster at pH 6.5 than at pH 7.4. The 5-FU-loaded nanocarrier had a long half-life after intravenous administration in mice and showed high tumor targeting. This nanocarrier composite also showed enhanced anticancer effects. PPD is a promising nanocarrier of anticancer drugs with high encapsulation, tumor targeting and pH-responsive release in tumors.
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
authors.forename: Xia
authors.initials: X
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Lijing
authors.initials: L
authors.lastname: Ke
authors.forename: Erjuan
authors.initials: E
authors.lastname: Ning
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.forename: Jeremy
authors.initials: J
authors.lastname: Bradshaw
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D009757:Nylons / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D050091:Dendrimers; D004337:Drug Carriers; D008689:Methacrylates; D009757:Nylons; C520550:PAMAM-G4; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C519537:diethylaminoethyl methacrylate; D005472:Fluorouracil