Doxorubicin (DOX)-loaded cationic liposomes (DOXL) coated by N-trimethyl chitosan (TMCs) has been previously shown to enhance DOX uptake by human umbilical vein endothelial cells (HUVECs) in vitro and the tumor inhibition on solid tumor in vivo, and the effects were both enhanced with the degree of quaternization (DQ) increase of TMCs. The aim of the present work is to study the cytotoxicity of the blank cationic liposomes (CLs) coated by TMCs with various DQ on L-929 mouse fibroblasts, by MTT assay, using the relative proliferation rate as the indicator, and the toxicity extent was classified according to the evaluation criteria of United States Pharmacopoeia. Furthermore, the in vivo tumor angiogenesis targeting of DOXL coated by TMC60 was studied. It was found that with the increase of TMCs concentration and DQ, cytotoxicity was increased accordingly. However, the cell proliferation rates of TMCs-coated CLs with TMCs concentrations of 0.02% and 0.05%(w/w) were all above 80%, even the concentration of TMC20 was increased to 0.2%(w/w), the cell proliferation rate was still above 80%, showing noncytotoxicity. The mouse H-22 tumor model was established by transplanted tumor experiment. In vivo fluorescence in tumor tissue was investigated through the tail vein injection of fluorescein isothiocyanate conjugated dextran at the 7th day after the administration of different DOX preparations. Compared with DOX solution and uncoated DOXL, the mice given TMC60-coated DOXL showed tumor angiogenesis with good shape, uniform arrangement, and small vascular branches, and the vascular density was decreased, suggesting promising tumor angiogenesis targeting of TMC60-coated DOXL. (C) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 128: 21-27, 2013