Lipoplatin, a liposomal formulation of
cisplatin, was developed with almost negligible nephrotoxicity,
ototoxicity and neurotoxicity, as demonstrated in preclinical and Phase I human studies. A
polyethylene-glycol coating of the
liposome nanoparticles is supposed to result in
tumor accumulation of the
drug by extravasation through the altered
tumor vasculature. We explored the hypothesis that
intravenous infusion of
Lipoplatin results in
tumor targeting in four independent patient cases (one with hepatocellular
adenocarcinoma, two with
gastric cancer and one with
colon cancer) who underwent
Lipoplatin infusion followed by a prescheduled surgery approximately 20 h later. Direct measurement of the
platinum levels in specimens from the excised
tumors and normal tissues showed that the total
platinum levels were on average 10-50 times higher in malignant tissue compared to the adjacent normal tissue specimens; most effective targeting was observed in
colon cancer, with an accumulation up to 200-fold higher in colon
tumors compared to normal colon tissue. Of the several surgical specimens, gastric
tumors displayed the highest levels of total
platinum suggesting
Lipoplatin as a candidate
anticancer agent for gastric
tumors; gastric
tumor specimens had up to 260 micrograms
platinum /g tissue, that was higher than any tissue level in animals treated at much higher doses. Fat tissue displayed a high accumulation of total
platinum in surgical specimens in three different patients, correlating to the
lipid capsule of
cisplatin in its
Lipoplatin formulation. It was also inferred that normal tissue had more
platinum trapped in the tissue but not reacted with macromolecules, whereas
tumor tissue displayed
platinum that reacted with cellular macromolecules; the data were consistent with a model where
Lipoplatin damages more
tumor compared to normal cells. In conclusion,
Lipoplatin has the ability to preferentially concentrate in malignant tissue both of primary and metastatic origin following
intravenous infusion to patients. In this respect,
Lipoplatin emerges as a very promising
drug in the arsenal of chemotherapeutics.