Document Detail


Intracellular photodynamic therapy with photosensitizer-nanoparticle conjugates: cancer therapy using a 'Trojan horse'.
MedLine Citation:
PMID:  16886087     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phthalocyanine-nanoparticle conjugates have been designed and synthesised for the delivery of hydrophobic photosensitizers for photodynamic therapy (PDT) of cancer. The phthalocyanine photosensitizer stabilized gold nanoparticles have an average diameter of 2-4 nm. The synthetic strategy interdigitates a phase transfer reagent between phthalocyanine molecules on the particle surface that solubilises the hydrophobic photosensitizer in polar solvents enabling delivery of the nanoparticle conjugates to cells. The phthalocyanine is present in the monomeric form on the nanoparticle surface, absorbs radiation maximally at 695 nm and catalytically produces the cytotoxic species singlet oxygen with high efficiency. These properties suggest that the phthalocyanine-nanoparticle conjugates are ideally suited for PDT. In a process that can be considered as cancer therapy using a 'Trojan horse', when the nanoparticle conjugates are incubated with HeLa cells (a cervical cancer cell line), they are taken up thus delivering the phthalocyanine photosensitizer directly into the cell interior. Irradiation of the nanoparticle conjugates within the HeLa cells induced substantial cell mortality through the photodynamic production of singlet oxygen. The PDT efficiency of the nanoparticle conjugates, determined using colorimetric assay, was twice that obtained using the free phthalocyanine derivative. Following PDT with the nanoparticle conjugates, morphological changes to the HeLa cellular structure were indicative of cell mortality via apoptosis. Further evidence of apoptosis was provided through the bioluminescent assay detection of caspase 3/7. Our results suggest that gold nanoparticle conjugates are an excellent vehicle for the delivery of surface bound hydrophobic photosensitizers for efficacious photodynamic therapy of cultured tumour cells.
Authors:
Martina E Wieder; Duncan C Hone; Michael J Cook; Madeleine M Handsley; Jelena Gavrilovic; David A Russell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-21
Journal Detail:
Title:  Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology     Volume:  5     ISSN:  1474-905X     ISO Abbreviation:  Photochem. Photobiol. Sci.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-03     Completed Date:  2007-08-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101124451     Medline TA:  Photochem Photobiol Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  727-34     Citation Subset:  IM    
Affiliation:
School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK NR4 7TJ.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  radiation effects
Drug Screening Assays, Antitumor
Gold / chemistry,  radiation effects
Hela Cells
Humans
Hydrophobicity
Indoles / chemistry,  pharmacokinetics*,  radiation effects
Light
Molecular Structure
Nanoparticles / chemistry*,  radiation effects
Neoplasms / drug therapy*
Organometallic Compounds / chemistry,  pharmacokinetics*,  radiation effects
Oxygen / metabolism
Photochemotherapy / methods*
Photosensitizing Agents / chemistry,  pharmacokinetics*,  radiation effects
Structure-Activity Relationship
Surface Properties
Chemical
Reg. No./Substance:
0/Indoles; 0/Organometallic Compounds; 0/Photosensitizing Agents; 14320-04-8/Zn(II)-phthalocyanine; 7440-57-5/Gold; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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