Synthesis and in vitro phototoxicity of multifunctional Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin-coated gold nanoparticles assembled via axial coordination with imidazole ligands

María E Alea-Reyes; Oriol Penon; Paula García Calavia; María J Marín; David A Russell; Lluïsa Pérez-García

doi:10.1016/j.jcis.2018.03.014

Synthesis and in vitro phototoxicity of multifunctional Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin-coated gold nanoparticles assembled via axial coordination with imidazole ligands

J Colloid Interface Sci. 2018 Jul 1:521:81-90. doi: 10.1016/j.jcis.2018.03.014. Epub 2018 Mar 7.

Authors

María E Alea-Reyes¹, Oriol Penon², Paula García Calavia³, María J Marín⁴, David A Russell⁵, Lluïsa Pérez-García⁶

Affiliations

¹ Departament de Farmacologia, Toxicologia i Química Terapèutica, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028 Barcelona, Spain; Institut de Nanociència i Nanotecnologia UB (IN2UB), Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028 Barcelona, Spain. Electronic address: malearey7@alumnes.ub.edu.
² Departament de Farmacologia, Toxicologia i Química Terapèutica, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028 Barcelona, Spain; Institut de Nanociència i Nanotecnologia UB (IN2UB), Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028 Barcelona, Spain. Electronic address: oriolpenon@gmail.com.
³ School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK. Electronic address: p.garcia-calavia@icenidiagnostics.com.
⁴ School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK. Electronic address: m.marin-altaba@uea.ac.uk.
⁵ School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK. Electronic address: D.Russell@uea.ac.uk.
⁶ Departament de Farmacologia, Toxicologia i Química Terapèutica, Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028 Barcelona, Spain; Institut de Nanociència i Nanotecnologia UB (IN2UB), Universitat de Barcelona, Avda. Joan XXIII 27-31, 08028 Barcelona, Spain. Electronic address: mlperez@ub.edu.

PMID: 29550701
DOI: 10.1016/j.jcis.2018.03.014

Abstract

Hypothesis: Metalloporphyrins are extensively investigated for their ability to form reactive oxygen species and as potent photosensitisers for use in photodynamic therapy. However, their hydrophobicity generally causes solubility issues concerning in vivo delivery due to lack of distribution and low clearance from the body. Immobilising porphyrins on carriers, such as gold nanoparticles (GNP), can overcome some of these drawbacks. The mode of assembling the porphyrins to the carrier influences the properties of the resulting drug delivery systems.

Experiments: We describe the synthesis and characterisation of new porphyrin decorated water soluble GNP and we explore Zn-imidazole axial coordination as the mode of linking the porphyrin to the metallic core of the nanoparticles. Quantification of singlet oxygen production, toxicity in dark, cellular uptake by SK-BR-3 cells and phototoxicity have been assessed.

Findings: Axial coordination limits the number of porphyrins on the gold surface, reduces the formation of aggregates, and diminishes metal exchange in the porphyrin, all of which contribute to enhance the efficiency of singlet oxygen generation from the immobilised porphyrin. In vitro experiments on SK-BR-3 cells reveal a fast uptake followed by more than 80% cell death after irradiation with low doses of light.

Keywords: Cellular uptake; Dark cytotoxicity; Gold nanoparticles; Imidazole ligands; Photodynamic therapy; Phototoxiciy; SK-BR-3 cells; Singlet oxygen production; Zn(II)-imidazole axial coordination; Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin.