Novel porphyrazine derivatives show promise for photodynamic therapy despite restrictions in hydrophilicity

Abstract

Complexing of ligands to photosensitizers (Ps) has gained popularity by enhancing solubility, cell-surface recognition and tissue specificity for applications in Photodynamic Therapy (PDT) and fluorescence-based diagnostics. Here we report on nine carbohydrate-functionalized porphyrazine (Pz-galactopyranose/methyl-ribose) derivatives bearing either H2, Zn(II) or Ni(II) cores for potential use in PDT. Derivatives proved soluble only in organic solvents; dichloromethane (DCM) and tetrahydrofuran (THF). Derivatives were subsequently solubilized using DCM-based PEG-DSPE 5000-PBS encapsulation for biological studies due to THF cytotoxicity. Absorption spectra analyses viewed no correlation between core ion, carbohydrate type and peripheral position though encapsulation efficiency (%EE) followed a general order of Zn(II) (60-92%) > Ni(II) (4-21%). As such, phototoxicity of Zn(II)Pz derivatives were far superior to H2Pz and Ni(II)Pz counterparts following 631.4 nm excitation of MCF-7 breast cancer cells. Variation was attributed to persistent aggregation and low %EE when regarding the absorption properties recorded. It is therefore believed that revision of the encapsulation method for H 2Pz and Ni(II)Pz derivatives would render improved phototoxicity. Zn(II)Pz derivatives show promise as agents for PDT of cancer. Complexing of ligands to photosensitizers (Ps) can enhance solubility, cell-surface recognition and tissue specificity for applications in Photodynamic Therapy (PDT). Nine carbohydrate-functionalized porphyrazine (Pz-galactopyranose/methyl- ribose) derivatives with H2, Zn(II) or Ni(II) cores were analyzed for potential use in PDT. Derivatives solubilized in DCM and tetrahydrofuran were cytotoxic; encapsulation in DCM-based PEG-DSPE5000-PBS was biologically suitable. No correlation between core ion, carbohydrate type and peripheral position was revealed via absorption spectra analyses. Encapsulation efficiency (%EE): Zn(II) (60-92%) > Ni(II) (4-21%). Phototoxicity of Zn(II)Pz derivatives showed highest efficiency following excitation in MCF-7 cells, and show promise as anticancer PDT agents. © 2014 The American Society of Photobiology.