Delivery of a hydrophobic phthalocyanine photosensitizer using PEGylated gold nanoparticle conjugates for the in vivo photodynamic therapy of amelanotic melanoma

Abstract

Photodynamic therapy (PDT) is a treatment of cancer whereby tumours are destroyed by reactive oxygen species generated upon photoactivation of a photosensitizer drug. Hydrophobic photosensitizers are known to be ideal for PDT; however, their hydrophobicity necessitates that they are typically administered using emulsions. Here, a delivery vehicle for photodynamic therapy based on the co-self-assembly of both a Zn(ii)-phthalocyanine derivative photosensitizer and a polyethylene glycol (PEG) derivative onto gold nanoparticles is reported. The PEG on the particle surface ensured that the conjugates were water soluble and enhanced their retention in the serum, improving the efficiency of PDT in vivo. The pharmacokinetic behaviour of the nanoparticle conjugates following intravenous injection into C57/BL6 mice bearing a subcutaneous transplanted B78H1 amelanotic melanoma showed a significant increase of retention of the nanoparticles in the tumour. PDT tumour destruction was achieved 3 h following injection of the nanoparticle conjugates leading to a remarkable 40% of the treated mice showing no tumour regrowth and complete survival. These results highlight that dual functionalised nanoparticles exhibit significant potential in PDT of cancer especially for difficult to treat cancers such as amelanotic melanoma.

Water soluble, multifunctional antibody-porphyrin gold nanoparticles for targeted photodynamic therapy

“…[16][17][18][19] PEG has also been used to provide water solubility and to enhance in vivo accumulation in the tumour tissue by the enhanced vascular permeability and retention effect of gold nanoparticles functionalised with a hydrophobic zinc phthalocyanine. 20 Furthermore, PEG can also be a key building block in the synthesis of nanosystems for targeted photodynamic therapy. Cancer cells that overexpress specific cell surface receptors can be selectively recognised by incorporating the corresponding targeting agents such as antibodies or lectins onto the surface of the nanoparticles.…”

Nanosystems for Improved Targeted Therapies in Melanoma

“…Gold nano-shells can also be used as photosensitizers in PDT. Due to their capacity to produce major reactive oxygen species for the photo-dynamic technique under NIR light, they consequently proved to suppress the proliferation of melanoma cells [77,78].…”

Using gold nanoparticles in diagnosis and treatment of melanoma cancer

“…Photodynamic therapy and electron microscopy studies revealed that the AuNPconjugated C11Pc could result in the reduction of tumour growth and destruction of the tumour vasculature, respectively. In another study by Camerin et al [112], hydrophobic phthalocyanine photosensitizer was conjugated with PEGylated AuNP. This photosensitizer is commonly applied to treatment of melanoma with reactive oxygen species on photodynamic technique.…”