In situ dose amplification by apoptosis-targeted drug delivery.

When tumor cells undergo apoptosis in response to chemotherapy, the levels of apoptotic biomarkers such as histone H1 are increased at the tumor. This would amplify in situ homing signals and thus drug delivery by apoptosis-targeted drugs. To examine this possibility, we prepared apoptosis-targeted liposomes containing doxorubicin by labeling them with the CQRPPR peptide (ApoPep-1) that recognizes apoptotic cells by binding to histone H1. ApoPep-1-labeled liposomes, but not folate-labeled liposomes, inhibited tumor growth in mice more efficiently than untargeted liposomes, although in vitro cytotoxicities of those liposomes were similar. Fluorescence imaging signals at tumor were increased by the homing of ApoPep-1-labeled, fluorescent liposomes, which was correlated with the increase of apoptosis and the amount of doxorubicin at the tumor and, conversely, with the decrease of tumor volume. These results demonstrate that the apoptosis-targeted drug delivery enables in situ dose amplification and, when combined with imaging of apoptosis, provides a real-time monitoring of treatment response for cancer theragnosis.