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

Abstract

Photodynamic therapy (PDT) is a treatment of cancer by which tumour cells are destroyed using reactive oxygen species produced by photosensitisers following activation with visible or near infrared light. Successful PDT depends on the solubility and the targeting ability of the photosensitisers. In this work, the synthesis of a porphyrin-based water soluble nanoparticle conjugate containing a targeting agent that recognises the erbB2 receptor overexpressed on the surface of particular cancer cells is reported. The nanoparticle conjugates were synthesised following two different protocols, viz. a biphasic and a monophasic method, with the aim to determine which method yielded the optimal nanosystem for potential PDT applications. The nanoparticles were characterised using UV-Vis absorption and fluorescence spectroscopies together with transmission electron microscopy and zeta potential measurements; and their ability to produce singlet oxygen following irradiation was investigated following the decay in absorption of a singlet oxygen probe. The nanoparticles synthesised using the monophasic method were shown to produce the highest amount of singlet oxygen and were further functionalised with anti-erbB2 antibody to target the erbB2 receptors expressed on the surface of SK-BR-3 human breast cancer cells. The water soluble, antibody-porphyrin nanoparticle conjugates were shown to elicit targeted PDT of the breast cancer cells.

Amphiphilic gemini pyridinium-mediated incorporation of Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin into water-soluble gold nanoparticles for photodynamic therapy

“…These results demonstrate that the porphyrin Na-ZnTCPP resulted more effective when immobilized on GNP rather than free in solution, with an increased singlet oxygen production, a feature previously reported for similar systems [2,33]. This fact is even more remarkable considering that the photobleaching of the porphyrin incorporated into GNP was measured in aqueous solution, where oxygen is much less soluble and usually leads to a less significant effect for this type of measurement because of the shorter lifetime of singlet oxygen in water [34].…”

“…PDT is an approach of cancer treatment based on the use of specific drugs, called photosensitizers, which can induce cell death after irradiation, due to the formation of reactive oxygen species [1][2][3]. PDT has several advantages in the treatment of cancer, since it is less invasive, minimizes the secondary effects and allows more localized areas of the body to be treated.…”

“…The major drawbacks of PDT are the non-specific distribution of the photosensitizer into the body, and the water-solubility of the photosensitizer, which can be low and thus requires a formulation to improve the administration. In particular, porphyrins are one of the most studied photosensitizers in the last years, to be applied in PDT [2,[4][5][6][7] but also in sensors as hosts for molecular recognition [8,9]. One of the main characteristics of the porphyrin's structure is the possibility to incorporate a metal into its core, in particular bivalent cations such as Zn 2+ , Mg 2+ , Co 2+ or Fe 2+ .…”

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy

“…The possibility to prepare a multicomponent system based on water-soluble AuNPs for PDT was recently reported by Peron et al (Penon et al 2017). This group constructed a nanoplatform of AuNPs (PS-AuNPs-PEG-Ab) containing a porphyrin derivative as PS and a polyethyleneglycol derivative linked to an anti-erbB2 antibody to specifically target the erbB2 receptors overexpressed on the surface of SK-BR-3 breast cancer cells ( Figure 14); the presence of the thiol groups in both ligands allowed a suitable functionalization of the AuNP.…”

“…Besides the high level of cellular uptake, changes in the cellular morphology were detected and cell membrane damages were confirmed after irradiation of the SK-BR-3 cancer cells when incubated with the PS-AuNP-PEG-Ab conjugate (Penon et al 2017). In 2016, Ferreira et al considered the use of two different shapes (spheres and rods) of gold nanostructures to prepare a colloidal hybrid system with the cationic derivative of 5,10,15,20-tetrapyridylporphyrin (Figure 2) to be used in PDT (Ferreira et al 2016).…”