Background: The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell
radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials.
Objective: To develop a targeted drug delivery and tracing System with pH-sensitive liposomes
(SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse
effects and to enable tracing under magnetic resonance.
Methods: SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method.
HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The
characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated.
Results: The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were
30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively
2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISOSpHLs
was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer.
SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were
packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve
showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were
compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and
SPION concentrations in culture medium showed significant differences between the same concentration
groups (P < 0.0001) and at different times (P < 0.0001).
Conclusion: SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and
thus provides a system for targeted delivery and tracing under magnetic resonance.