Document Detail

Tumor cell apoptosis induced by nanoparticle conjugate in combination with radiation therapy.
MedLine Citation:
PMID:  21030759     Owner:  NLM     Status:  In-Process    
Semiconductor nanoparticles conjugated to photosensitizers have been shown to increase tumor cell death with ionizing radiation but the mechanism, particularly the role of photodynamic therapy in the process, was unknown. We used a molecular probe to measure production of (1)O(2) to quantify the component of photodynamic cell-killing in an in vitro system. The intracellular distribution of the nanoparticle conjugate (NC) was determined by the co-localization of nanoparticles and the lysotracker. Induction of apoptosis was measured by the TUNEL assay and western blot analysis of the cleaved caspase-3. As a result, dose-dependent (1)O(2) production was observed with 48 nm NC after irradiating with 6 MV x-rays. A high geometrical coincidence between the fluorescence emission of the nanoparticle and lysotracker was observed using confocal microscopy. Finally, apoptosis, as indicated by the TUNEL stain and cleavage of the caspase-3, was observed in cells treated by both the NC and 6 Gy of radiation but not in cells treated with radiation alone. In conclusion, the cell death induced by the NC in combination with radiation is consistent with a supra-additive effect to radiation-or NC-alone-killing and is mediated by an NC-induced photodynamic therapy mechanism, which is distinctly different from that for radiation-killing alone. By providing a second distinct cell-killing mechanism, this nanoparticle conjugate has great promise as a targeted physical radiosensitizer aimed at overcoming radioresistant tumor clonogens or/and reducing normal tissue toxicity by using a lower ionizing radiation dose.
Li Wang; Wensha Yang; Paul Read; James Larner; Ke Sheng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-29
Journal Detail:
Title:  Nanotechnology     Volume:  21     ISSN:  1361-6528     ISO Abbreviation:  Nanotechnology     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101241272     Medline TA:  Nanotechnology     Country:  England    
Other Details:
Languages:  eng     Pagination:  475103     Citation Subset:  IM    
Department of Radiation Oncology, University of Virginia, Virginia, USA.
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