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Nuclisome :
Nuclisome : a novel concept for radionuclide therapy using targeting liposomes
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- Fondell, Amelie (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Edwards, Katarina (författare)
- Uppsala universitet,Fysikalisk kemi
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- Ickenstein, Ludger M (författare)
- Uppsala universitet,Fysikalisk kemi
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- Sjöberg, Stefan (författare)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
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- Carlsson, Jörgen (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Gedda, Lars (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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(creator_code:org_t)
- 2009-08-07
- 2010
- Engelska.
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 37:1, s. 114-123
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- PURPOSE: For the treatment of cancer, the therapeutic potential of short-range, low-energy Auger-electron emitters, such as (125)I, is getting progressively wider recognition. The potency of Auger-electron emitters is strongly dependent on their location in close vicinity to DNA. We have developed a new two-step targeting strategy to transport (125)I into cancer-cell nuclei using PEG-stabilized tumour-cell targeting liposomes named "Nuclisome-particles". METHODS: In the present study, epidermal growth factor (EGF) was used as a tumour-cell-specific agent to target the EGF-receptor (EGFR) and the liposomes were loaded with (125)I-Comp1, a recently synthesized daunorubicin derivative. RESULTS: As analysed with cryo-TEM, the derivative precipitates inside liposomes at a drug-to-lipid molar ratio of 0.05:1. Receptor-specific uptake in cultured U-343MGaCl2:6 tumour cells of EGFR-targeting liposomes increased with time while non-specific and receptor-blocked uptake remained low. Nuclisome-particles were able to target single U-343MGaCl2:6 cells circulating in human blood during 4 h, with low uptake in white blood cells, as demonstrated in an ex vivo system using a Chandler loop. Autoradiography of targeted cells indicates that the grains from the radiolabelled drug are mainly co-localized with the cell nuclei. The successful targeting of the nucleus is shown to provide high-potency cell killing of cultured U-343MGaCl2:6 cells. At the concentration used, Nuclisome-particles were up to five orders of magnitude more effective in cell killing than EGFR-targeting liposomes loaded with doxorubicin. CONCLUSION: The results thus provide encouraging evidence that our two-step targeting strategy for tumour cell DNA has the potential to become an effective therapy against metastasizing cancer cells in the bloodstream.
Nyckelord
- Targeting liposomes
- EGF
- Radionuclide therapy
- Anthracyclines
- Auger-electron emitter
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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