Targeted liposomes for cell death imaging and amplified drug delivery

Download
2013-03-02
RİCE, Douglas
Türkyılmaz, Serhan
PALUMBO, Rachael
HARMATYS, Kara
SMİTH, Bradley D
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.

Suggestions

Structural and functional damages of whole body ionizing radiation on rat brain homogenate membranes and protective effect of amifostine
ÇAKMAK, GÜLGÜN; Severcan, Mete; Zorlu, Faruk; Severcan, Feride (Informa UK Limited, 2016-01-01)
Purpose: To investigate the effects of whole body ionizing radiation at a sublethal dose on rat brain homogenate membranes and the protective effects of amifostine on these systems at molecular level.
Forward problem solution for electrical conductivity imaging via contactless measurements
Gençer, Nevzat Güneri (IOP Publishing, 1999-04-01)
The forward problem of anew medical imaging system is analysed in this study. This system uses magnetic excitation to induce currents inside a conductive body and measures the magnetic fields of the induced currents. The forward problem, that is determining induced currents in the conductive body and their magnetic fields, is formulated. For a general solution of the forward problem, the finite element method (FEM) is employed to evaluate the scalar potential distribution. Thus, inhomogeneity and anisotropy...
Processing Turkish radiology reports
Hadımlı, Kerem; Üçoluk, Göktürk; Turhan Yöndem, Meltem; Department of Computer Engineering (2011)
Radiology departments utilize various visualization techniques of patients’ bodies, and narrative free text reports describing the findings in these visualizations are written by medical doctors. The information within these narrative reports is required to be extracted for medical information systems. Turkish is an highly agglutinative language and this poses problems in information retrieval and extraction from Turkish free texts. In this thesis one rule-based and one data-driven alternate methods for inf...
Determination of hydrate formation conditions of drilling fluids
Kupeyeva, Aliya; Parlaktuna, Mahmut; Department of Petroleum and Natural Gas Engineering (2007)
The objective of this study is to determine hydrate formation conditions of a multicomponent polymer based drilling fluid. During the study, experimental work is carried out by using a system that contains a high-pressure hydrate formation cell and pressure-temperature data is recorded in each experiment. Different concentrations of four components of drilling fluid, namely potassium chloride (KCl), partially hydrolyzed polyacrylicamide (PHPA), xanthan gum (XCD) and polyalkylene glycol (poly.glycol) were us...
Investigation of docetaxel and doxorubicin resistance in mcf-7 breast carcinoma cell line
Darcansoy İşeri, Özlem; Gündüz, Ufuk; Department of Biotechnology (2009)
Multidrug resistance phenotype of tumor cells describes resistance to wide range of structurally unrelated anticancer agents and is a serious limitation to effective chemotherapy. It is a multifactor yet not fully elucidated phenomenon by the involvement of diverse cellular pathways. Aim of this study was to investigate the resistance mechanisms developed against docetaxel and doxorubicin that are widely used in the treatment of breast cancer in model cell line MCF-7. Resistant sublines were developed by ap...
Citation Formats
D. RİCE, S. Türkyılmaz, R. PALUMBO, K. HARMATYS, and B. D. SMİTH, “Targeted liposomes for cell death imaging and amplified drug delivery,” 2013, vol. 54, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/42176.