Show/Hide Menu
Hide/Show Apps
anonymousUser
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Frequently Asked Questions
Frequently Asked Questions
Communities & Collections
Communities & Collections
Targeted liposomes for cell death imaging and amplified drug delivery
Download
index.pdf
Date
2013-03-02
Author
RİCE, Douglas
Türkyılmaz, Serhan
PALUMBO, Rachael
HARMATYS, Kara
SMİTH, Bradley D
Metadata
Show full item record
This work is licensed under a
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
.
Item Usage Stats
7
views
5
downloads
The goal is to develop liposomes that have selective affinity for dead and dying cells, and then use the liposomes as targeted imaging agents for rapidly assessing the efficacy of anticancer therapies. A subsequent application is to use the liposomes to deliver anticancer drugs to tumors and initiate cell death processes that amplify the liposome targeting at later time points in the therapy. The liposome surface is decorated with 2% Zn-DPA-PEG2000-PE, an anchored phospholipid with an extended polyethylene chain that terminates with a zinc-dipicolylamine (Zn-DPA) targeting group. Previous studies with fluorescent Zn-DPA molecular probes have shown that they have high selective affinity for dead and dying cells. Specifically, they target the anionic phospholipid, phosphatidylserine (PS), a cell death biomarker that is exposed on the surface of dead and dying cells. Zn-DPA liposomes are composed of 2% Zn-DPA-PEG2000-PE, 67% 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 30% cholesterol and 1% near-infrared fluorophore (DiR). Untargeted liposomes are composed of 69% POPC, 30% cholesterol and 1% DiR. The ability of Zn-DPA liposomes to target a chemical model of the PS cell death biomarker was assessed using a fluorescence quenching assay. These studies revealed that the PEG chains do not inhibit the affinity of the Zn-DPA units. In vitro fluorescence microscopy of several cancer model cell-lines (MDA-MB-213, Jurkat E6-1) showed that the Zn-DPA liposomes strongly stain dead and dying cancer cells that were treated with the anticancer agent etoposide. Multicolor imaging of dead and dying cells using the small molecule DPA probe PSVue™480 demonstrates that Zn-DPA liposomes co-localize to the dead cell periphery, a definitive feature of surface targeting. A rat thymus atrophy model was used to access the in vivo cell death targeting capability of Zn-DPA liposomes. Rats were dosed with intraperitoneal dexamethasone to induce thymocyte cell death. Zn-DPA and untargeted liposomes were intravenously injected into separate cohorts (n = 3) and after 24 hours, the rats were euthanized and their organs were excised and imaged. The uptake of targeted liposomes into the dying tissue was more than 4-fold greater than the untargeted liposome system. In summary, liposomes coated with multiple copies of Zn-DPA targeting groups are effective cell death imaging agents for fluorescence microscopy and they can target dead and dying tissue in living animals. With further development, these targeted liposomes have potential utility for rapid clinical evaluation of anticancer drug efficacy in individual patients.
Subject Keywords
Radiology
URI
https://hdl.handle.net/11511/42176
DOI
https://doi.org/10.2967/jnm542abs
Collections
Department of Chemistry, Conference / Seminar