Liposomes, capable of temperature-triggered content release at the site of interest, can be of great importance for imaging and
therapy of
tumors. The delivery of imaging agents or
therapeutics can be improved by application of
liposomes with a gel-to-liquid phase-transition temperature suitable for mild
hyperthermia (41-43°C), and by prolonging their circulation time by incorporation of
lipids containing polyethyleneglycol moieties. Still, the rapid wash out of the delivered material from the
tumor tissue is a major obstacle for both imaging and
therapy. In this study, we developed an optimized temperature sensitive liposomal system to be used with mild
hyperthermia: highly stable at physiological temperature and with a sharp transition of the bilayer at 41.5°C, with subsequent rapid release of entrapped compounds such as
calcein or
tumor cell-targeting
contrast agents. Intravital microscopy on
calcein/
rhodamine containing
liposomes was applied to demonstrate the applicability of this system in vivo. The
calcein loaded
liposomes were injected iv into nude mice with a human BLM
melanoma tumor implanted in a dorsal skin-fold window chamber. Arrival of the
liposomes at the
tumor site and content release after temperature increase were monitored. The results demonstrated not only accumulation of the
liposomes at the
tumor site, but also a massive release of
calcein after increase of the temperature to 41°C. The versatility of the thermosensitive
liposomes was further demonstrated by encapsulation of a
tumor cell-targeting
DOTA-
phenylboronate conjugate and its release at elevated temperatures. The
DOTA ligand in this system is able to chelate a variety of metals suitable for both diagnostic and therapeutic applications, whereas the
phenylboronate function is able to target specifically to
tumor cells through a covalent binding with
sialic acid moieties over-expressed on their surface upon heat-triggered release from the liposomal carrier.