Abstract
We recently designed a PEG-coated cationic liposome targeted to angiogenic vessels and showed, in a murine dorsal air sac model, potent anti-angiogenic activity of an oxaliplatin (I-OHP) formulation of this liposome in. the present study, we extended the I-OHP formulation to a murine tumor-xenograft model. Following three injections, I-OHP containing PEG-coated cationic liposomes showed substantial tumor growth suppression and increased survival time of tumor-bearing mice without apparent side effects, compared with other I-OHP containing PEG-coated neutral liposomes and free I-OHP. In vivo imaging showed a preferential tumor accumulation and a broader distribution of PEG-coated cationic liposomes, compared with PEG-coated neutral liposomes. In addition, PEG-coated cationic liposomes delivered larger amounts of I-OHP into the tumor tissue than other I-OHP formulations, correlating with its antitumor efficiency. In vitro studies indicated that PEG-coated cationic liposomes were internalized not only by tumor cells but also by endothelial cells, and consequently its I-OHP formulation displayed higher cytotoxicity towards both cell types as compared with I-OHP containing PEG-coated neutral liposomes. In summary, I-OHP containing PEG-coated cationic liposomes induced significant tumor growth suppression, presumably by delivering encapsulated I-OHP into both tumor endothelial cells and tumor cells. Such dual targeting approach, i.e. vascular-targeting and tumor-targeting with a single liposomal I-OHP formulation, may have great potential for overcoming some major limitations in conventional chemotherapy. (c) 2009 Elsevier B.V. All rights reserved.