Tumor-specific delivery and therapy by double-targeted DTX-CMCS-PEG-NGR conjugates.

Abstract

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.

• Authors: Fengxi Liu, Min Li, Chunxi Liu, Yongjun Liu, Yanchao Liang, Fengshan Wang, Na Zhang
• Journal: Pharmaceutical research (Pharm Res) Vol. 31 Issue 2 Pg. 475-88 (Feb 2014) ISSN: 1573-904X [Electronic] United States
• PMID: 24043295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Taxoids
• carboxymethyl-chitosan
• Docetaxel
• Chitosan
• CD13 Antigens

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• CD13 Antigens (metabolism)
• Cell Line
• Cell Line, Tumor
• Chitosan (analogs & derivatives, chemistry, pharmacology)
• Docetaxel
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Drug Stability
• Endothelial Cells (metabolism)
• Hep G2 Cells
• Human Umbilical Vein Endothelial Cells
• Humans
• Melanoma, Experimental
• Mice
• Nanoparticles (chemistry)
• Taxoids (chemistry, pharmacology)