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The in vivo bioimaging using PET (positron emission tomography) to determine the delivery of novel cancer therapeutic constructs

Project Description

PhD project aims
Our previous data have proved that thermo-chemotherapy (TC) is far more effective than either hyperthermia or chemotherapy alone. The aim for this project is to use radiotracer for in vivo biodistribution study of the magnetic liposomes and magnetic nanoparticles. Liposomes will be radiolabelled using ionophores for metallic nuclides such as 89Zr, 52Mn and/or 64Cu and using novel methods developed by Dr. T.M. de Rosales that will allow to identify and quantify their biodistribution in vivo, and at the whole body level, using murine models of breast cancer using preclinical positron emission tomography (PET) imaging at KCL.
The student will synthesise magnetic nanoflowers, which have high heating efficiency. The synthetic procedure has already been optimized in the Prof Thanh’s lab.
Magnetic liposome formulation and characterization
The liposomes were prepared with the thin film hydration method. Then the magnetic nanoflowers were dissolved in citric buffer (pH 4.0) and mixed with gemcitabine (anticancer drug). The un-encapsulated Fe2O3 particles and gemcitabine in the liposomes, were removed by Sephadex G-25 gel filtration with HEPES buffer (pH 7.4). Subsequently, the doxorubicin was added to the previous solution at a molar ratio of 1:5. Free drug will be removed via the gel column.
Dynamic light scattering will be used for measuring the hydrodynamic diameter of the encapsulated liposome. Phosphate lipid concentrations were calculated by using phospholipid assay kit (Sigma life science, UK). Spectrophotometry was used for measuring the drugs concentration of the liposome. In order to extract the drugs from the liposome, 1% triton X-100 was used to dilute the liposomes and the mixture was heated above 90 °C for 5minutes. Once the sample was cooled down to room temperature, the absorbance at 480nm for doxorubicin was acquired by a UV-VIS spectrophotometer. The iron content of the liposome was determined by phenatroline colorimetric assay.
Cell culture experiments
The human breast adenocarcinoma cell lines MCF-7/wt, MDA-MB-231 and JIMT-1 will be used to test different liposome constructs containing MNPs, anticancer drugs to establish the right dose before the invivo experiments.
Bioimaging experiments
Liposomes will be radiolabelled using PET isotopes and established methods. Their stabilities in human serum will be studied prior to in vivo studies using murine models of breast cancer (MDA-MB-231 and/or MCF-7) and preclinical PET-CT. The pharmacokinetics and biodistribution over time of the liposomes will be obtained from these studies.

Funding Notes

Stipend starts at £16,180 pa.
The position is only available to EU students who lives in UK for 3 years or UK students. Oversea students with their own funding for tuition fee and bench fee can apply.

How good is research at University College London in Chemistry?

FTE Category A staff submitted: 62.00

Research output data provided by the Research Excellence Framework (REF)

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