Tumor-Specific Delivery and Therapy by Double-Targeted DTX-CMCS-PEG-NGR Conjugates

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• 作者：Fengxi Liu (1) (2)
  Min Li (1)
  Chunxi Liu (1)
  Yongjun Liu (1)
  Yanchao Liang (1)
  Fengshan Wang (1)
  Na Zhang (1) (2)
  
• 关键词：Carboxymethyl chitosan ; cNGR ; Docetaxel ; Double ; targeted ; Polymer ; drug conjugates
• 刊名：Pharmaceutical Research
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：31
• 期：2
• 页码：475-488
• 全文大小：1,013 KB
• 作者单位：Fengxi Liu (1) (2)
  Min Li (1)
  Chunxi Liu (1)
  Yongjun Liu (1)
  Yanchao Liang (1)
  Fengshan Wang (1)
  Na Zhang (1) (2)
  
  1. The School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji’nan, Shandong Province, 250012, China
  2. School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji’nan, Shandong Province, 250012, People’s Republic of China
  
• ISSN：1573-904X

文摘

Purpose 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.