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

Ongarora BG, Hu X, Verberne-Sutton SD, Garno JC, Vicente MG - Theranostics (2012)

Bottom Line: The most phototoxic compounds were found to be the α-substituted Pcs.The β-substituted ZcPcs 6b and 4b accumulated the most within HEp2 cells but had low photocytoxicity (IC(50) > 100 μM at 1.5 J/cm(2)), 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.

View Article: PubMed Central - PubMed

Affiliation: Louisiana State University, Department of Chemistry, Baton Rouge LA, 70803, USA.

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 (IC(50) ca. 10 μM at 1.5 J/cm(2)), 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 (IC(50) > 100 μM at 1.5 J/cm(2)), 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.

No MeSH data available.


Related in: MedlinePlus

(a) Absorption and (b) fluorescence spectra for Pc 4a (red), 4b (green), 6a (black), 6b (brown), 9a (grey), 9b (purple), 11a (light green), 11b (orange), 16b (blue), 16a (pink), at 8.0 and 0.5-0.8 μM concentrations, respectively, in DMF.
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Figure 2: (a) Absorption and (b) fluorescence spectra for Pc 4a (red), 4b (green), 6a (black), 6b (brown), 9a (grey), 9b (purple), 11a (light green), 11b (orange), 16b (blue), 16a (pink), at 8.0 and 0.5-0.8 μM concentrations, respectively, in DMF.

Mentions: The spectroscopic properties of the di-cationic ZnPcs 4a,b, 6a,b, 9a,b, 11a,b, 16a,b and their amine precursors in DMF are summarized in Table 1 and shown in Figure 2. No aggregation of the Pcs was apparent up to 10 μM concentrations in DMF 42. All ZnPcs showed strong Q absorptions and emissions in the near-IR between 679-686 nm in DMF, with small Stokes' shifts between 2-4 nm, as is characteristic of this type of macrocycle 35,41-43. All the ZnPcs show a Soret absorption between 330 - 360 nm, a strong Q band between 677-683 nm and a vibrational band at around 620 nm, that strictly follow the Lambert-Beer law. The ZnPcs had fluorescence quantum yields in the range 0.09-0.23 in DMF, as expected for this type of compound 35,41-43.


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

Ongarora BG, Hu X, Verberne-Sutton SD, Garno JC, Vicente MG - Theranostics (2012)

(a) Absorption and (b) fluorescence spectra for Pc 4a (red), 4b (green), 6a (black), 6b (brown), 9a (grey), 9b (purple), 11a (light green), 11b (orange), 16b (blue), 16a (pink), at 8.0 and 0.5-0.8 μM concentrations, respectively, in DMF.
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Related In: Results  -  Collection

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Figure 2: (a) Absorption and (b) fluorescence spectra for Pc 4a (red), 4b (green), 6a (black), 6b (brown), 9a (grey), 9b (purple), 11a (light green), 11b (orange), 16b (blue), 16a (pink), at 8.0 and 0.5-0.8 μM concentrations, respectively, in DMF.
Mentions: The spectroscopic properties of the di-cationic ZnPcs 4a,b, 6a,b, 9a,b, 11a,b, 16a,b and their amine precursors in DMF are summarized in Table 1 and shown in Figure 2. No aggregation of the Pcs was apparent up to 10 μM concentrations in DMF 42. All ZnPcs showed strong Q absorptions and emissions in the near-IR between 679-686 nm in DMF, with small Stokes' shifts between 2-4 nm, as is characteristic of this type of macrocycle 35,41-43. All the ZnPcs show a Soret absorption between 330 - 360 nm, a strong Q band between 677-683 nm and a vibrational band at around 620 nm, that strictly follow the Lambert-Beer law. The ZnPcs had fluorescence quantum yields in the range 0.09-0.23 in DMF, as expected for this type of compound 35,41-43.

Bottom Line: The most phototoxic compounds were found to be the α-substituted Pcs.The β-substituted ZcPcs 6b and 4b accumulated the most within HEp2 cells but had low photocytoxicity (IC(50) > 100 μM at 1.5 J/cm(2)), 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.

View Article: PubMed Central - PubMed

Affiliation: Louisiana State University, Department of Chemistry, Baton Rouge LA, 70803, USA.

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 (IC(50) ca. 10 μM at 1.5 J/cm(2)), 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 (IC(50) > 100 μM at 1.5 J/cm(2)), 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.

No MeSH data available.


Related in: MedlinePlus