title: Tumor-specific delivery and therapy by double-targeted DTX-CMCS-PEG-NGR conjugates.
abstract: OBJECTIVE
  To synthesize and evaluate the antitumor efficacy of double-targeted docetaxel (DTX)-carboxymethyl chitosan (CMCS)-PEG-NGR (DTX-CPN) conjugates that could target to CD13 over-expressed tumor neovascular endothelium cells and tumor cells.
  
  
  METHODS
  DTX was conjugated to CMCS via biodegradable linker and cNGR was applied to endow the conjugates with double targeting ability. The physiochemical properties and stability of this DTX-CPN conjugates were characterized. Cellular uptake study was carried out to evaluate the targeting ability of DTX-CPN conjugates. Cytotoxicity and apoptosis analysis were conducted to evaluate in vitro antitumor effects. In vivo antitumor efficacy was investigated in B16 murine melanoma model.
  
  
  RESULTS
  DTX-CPN conjugates could self-assemble into nanoparticles in water and were stable in plasma. cNGR modification could promote the cellular uptake of DTX-CPN conjugates in CD13 positive HUVEC and B16 cells, leading to more significant cytotoxicity and apoptosis effect than non-targeted conjugates. DTX-CPN conjugates also exhibited better antitumor effect than non-targeted conjugates and Duopafei® in a B16 murine melanoma model.
  
  
  CONCLUSIONS
  Double-targeted DTX-CPN conjugates could efficiently target to tumor neovascular cells and tumor cells, and achieve good antitumor effects. DTX-CPN conjugates may be promising candidate for one-double targeting cancer therapy.
authors.affiliation: The School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Fengxi
authors.initials: F
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Liang
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018826:CD13 Antigens / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D042783:Endothelial Cells / Q000378:metabolism; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D043823:Taxoids; C514968:carboxymethyl-chitosan; D000077143:Docetaxel; D048271:Chitosan; D018826:CD13 Antigens
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