Wieder Martina E, Hone Duncan C, Cook Michael J, Handsley Madeleine M, Gavrilovic Jelena, Russell David A
School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK NR4 7TJ.
Photochem Photobiol Sci. 2006 Aug;5(8):727-34. doi: 10.1039/b602830f. Epub 2006 Jun 21.
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.
酞菁-纳米颗粒缀合物已被设计并合成,用于递送疏水性光敏剂以进行癌症的光动力疗法(PDT)。酞菁光敏剂稳定化的金纳米颗粒平均直径为2 - 4纳米。合成策略是在颗粒表面的酞菁分子之间插入一种相转移试剂,该试剂可使疏水性光敏剂在极性溶剂中溶解,从而使纳米颗粒缀合物能够递送至细胞。酞菁以单体形式存在于纳米颗粒表面,在695纳米处有最大吸收,并能高效催化产生细胞毒性物质单线态氧。这些特性表明酞菁-纳米颗粒缀合物非常适合用于光动力疗法。在一个可被视为使用“特洛伊木马”进行癌症治疗的过程中,当纳米颗粒缀合物与HeLa细胞(一种宫颈癌细胞系)孵育时,它们会被摄取,从而将酞菁光敏剂直接递送至细胞内部。对HeLa细胞内的纳米颗粒缀合物进行照射,通过单线态氧的光动力产生诱导了大量细胞死亡。使用比色法测定,纳米颗粒缀合物的光动力疗法效率是使用游离酞菁衍生物时的两倍。在用纳米颗粒缀合物进行光动力疗法后,HeLa细胞结构的形态变化表明细胞通过凋亡死亡。通过对caspase 3/7的生物发光测定提供了凋亡的进一步证据。我们的结果表明,金纳米颗粒缀合物是用于递送表面结合的疏水性光敏剂以对培养的肿瘤细胞进行有效光动力疗法的优良载体。