Abstract 5485: Apoptosis-targeted cell and drug delivery to tumor.

Abstract

Abstract When tumor cells undergo apoptosis in response to chemotherapy, the levels of apoptotic biomarkers such as phosphatidylserine and histone H1 are increased at the cell surface. Here we hypothesized that the chemotherapy-induced apoptosis would amplify in situ apoptotic biomarkers (homing signals) for apoptosis-targeted drug carriers and enhance drug delivery. To examine this possibility, we employed a phage display-identified CQRPPR peptide (ApoPep-1) as a targeting moiety, which was able to recognize apoptotic cells by binding to histone H1 on the surface of apoptotic cells. When injected into tumor-bearing mice, ApoPep-1-labeled, fluorescent liposomes containing doxorubicin inhibited tumor growth more efficiently than untargeted or folate-labeled liposomes. Moreover, in vivo fluorescence imaging could enable monitoring of tumor response during the chemotherapy. The imaging signals at tumor were increased by the homing of apoptosis-targeted liposomes, which was correlated with the increase of apoptosis and the amount of doxorubicin (payloads) at the tumor and, conversely, with the decrease of tumor volume. Next, we harnessed the chemotherapy-induced apoptosis of tumor cells as a homing signal for the delivery of apoptosis-targeted T cells to tumor. When labeled with ApoPep-1 using an oleyl acid-derived membrane anchor, targeted T cells preferentially bound to apoptotic tumor cells over living cells. In vivo imaging showed higher levels of tumor homing of targeted, fluorescent T cells in mice treated with chemotherapy more than those of untargeted T cells. These results demonstrate that the apoptosis-targeted delivery can efficiently enhance the delivery of cells or drugs to tumor and, when combined with imaging of apoptosis, provides a real-time monitoring of tumor response for cancer theragnosis. Citation Format: Lianhua Chi, Napoleon Bonaparte, Rang-woon Park, In-san Kim, Byung-heon Lee. Apoptosis-targeted cell and drug delivery to tumor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5485. doi:10.1158/1538-7445.AM2013-5485