Metastasis is still the most serious reason for the high mortality of
cancer patients. It is a complex process in which platelets play a crucial role. Several attempts have been performed to inhibit the metastatic process, some of these using modified
liposomes. The aggregation behaviour of human platelets and HT29 colon
carcinoma cells in the presence of
liposomes with a modified surface has been investigated in the present study.
Liposomes (PC/CH/
DMPE) were unmodified, sterically stabilized by
polyethylene glycol (
PEG-DSPE), or equipped with the
carbohydrate ligand sialyl Lewis(X) (conjugated to PEG-
DMPE or
DMPE as anchor) intended to specifically compete with
ligands expressed by HT29 cells. We found in vitro that an addition of surface modified
liposomes to human platelets in plasma caused an up to 2.9-fold increase in platelet aggregation. In addition, when HT29
tumor cells were mixed with platelets and surface modified
liposomes, the number of
tumor cells found in aggregates increased significantly from 8.3 % (only
tumor cells) to 30.2 %. This result was supported by fluorescence micrographs demonstrating a strong association of platelets and
liposomes around the
tumor cells. In addition, a clear decrease in number and a change in the distribution of
metastases after
intravenous injection of HT29 cells in combination with
liposomes was observed in vivo. While in control mice
metastases in lung, liver and in intestine were prevailing, liposomal treatment resulted in a new localization of
metastases in muscles. Taking together, the ability of surface modified
liposomes to enhance aggregate formation of platelets and
tumor cells has been demonstrated for the first time. The capability of these vesicles to interfere with the metastatic process might have implications for the use of such
liposomes for therapeutic applications.