Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells

Abstract

Di-cationic Zn(II)-phthalocyanines (ZnPcs) are promising photosensitizers for the photodynamic therapy (PDT) of cancers and for photoinactivation of viruses and bacteria. Pegylation of photosensitizers in general enhances their water-solubility and tumor cell accumulation. A series of pegylated di-cationic ZnPcs were synthesized from conjugation of a low molecular weight PEG group to a pre-formed Pc macrocycle, or by mixed condensation involving a pegylated phthalonitrile. All pegylated ZnPcs were highly soluble in polar organic solvents but were insoluble in water; they have intense Q absorptions centered at 680 nm and fluorescence quantum yields of ca. 0.2 in DMF. The non-pegylated di-cationic ZnPc 6a formed large aggregates, which were visualized by atomic force microscopy. The cytotoxicity, cellular uptake and subcellular distribution of all cationic ZnPcs were investigated in human carcinoma HEp2 cells. The most phototoxic compounds were found to be the α-substituted Pcs. Among these, Pcs 4a and 16a were the most effective (IC50 ca. 10 μM at 1.5 J/cm2), in part due to the presence of a PEG group and the two positive charges in close proximity (separated by an ethylene group) in these macrocycles. The β-substituted ZcPcs 6b and 4b accumulated the most within HEp2 cells but had low photocytoxicity (IC50 > 100 μM at 1.5 J/cm2), possibly as a result of their lower electron density of the ring and more extended conformations compared with the α-substituted Pcs. The results show that the charge distribution about the Pc macrocycle and the intracellular localization of the cationic ZnPcs mainly determine their photodynamic activity.

Cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms

“…Meanwhile, Che et al found that Au(III) complexes containing N-heterocyclic carbene ligands could be the thiol "switch-on" fluorescent probes and anti-cancer agents [31], while Parker et al observed the selective staining of chromosomal DNA in dividing cells using a luminescent Tb(III) complex [32]. Importantly, Vicente et al found that the intracellular localization of the Zn(II)-phthalocyanines determined their photodynamic activity [33]. However, relationship between their anticancer efficacy and localization need further elucidation.…”

Mini-review: fluorescence imaging in cancer cells using dye-doped nanoparticles

“…80,[82][83][84] However, a new phthalocyanine chemistry was used to create a series of PEGylated cationic molecules, which has promising in vitro behavior against cancer cells. 85 Click reactions have been employed to create phthalocyanines with different architectures; 4-arm star polymers utilizing either polystyrene or poly(tert-butyl acrylate) were synthesized with symmetrically tetra terminal alkynyl-substituted phthalocyanines as the core. The central metal atom in these systems was either copper or zinc.…”

Synthesis of Glycoconjugated Phthalonitriles for New Phthalocyanine-Based Photosensitizers

“…4). Due to the electronic effect and steric hindrance of 1,2-dibromoethane (11), no substitution products with galactopyranose 2 were obtained. 1,2:3,4-di-O-Isopropylidene-α-D-galactopyranose (2) was recovered quantitatively after workup (Sch.…”

“…Therefore, scientific attention has been focused on the development of water-soluble PSs. [8][9][10][11][12][13] The combination of the hydrophobic macrocycles with hydrophilic carbohydrate moieties has attracted a great deal of attention, mainly due to the fact that several carbohydrates have a specific recognition for cancer cells. [14][15][16] In addition, these carbohydrate residues enhance the solvation properties of the photosensitizer to ensure more effective photocytotoxic activity.…”