Intracellular photodynamic therapy with photosensitizer-nanoparticle conjugates: cancer therapy using a 'Trojan horse'.
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.
Wieder
Martina E
ME
School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK NR4 7TJ.
Hone
Duncan C
DC
Cook
Michael J
MJ
Handsley
Madeleine M
MM
Gavrilovic
Jelena
J
Russell
David A
DA
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000528:radiation effects; D054833:Isoindoles; D008027:Light; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000528:radiation effects; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000528:radiation effects; D013329:Structure-Activity Relationship; D013499:Surface Properties; D017967:Zinc Compounds
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D006046:Gold; D010100:Oxygen