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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

Side-by-side comparison of sample aggregation on surfaces of mica(0001). Topography images of Pcs (A) 6a, (B) 2b, and (C) 16a, with corresponding cursor profiles. The frame sizes are 2 × 2 µm2, acquired in ambient air using tapping-mode AFM.
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Figure 1: Side-by-side comparison of sample aggregation on surfaces of mica(0001). Topography images of Pcs (A) 6a, (B) 2b, and (C) 16a, with corresponding cursor profiles. The frame sizes are 2 × 2 µm2, acquired in ambient air using tapping-mode AFM.

Mentions: All di-cationic ZnPcs 4a,b, 6a,b, 9a,b, 11a,b, and 16a,b are soluble in polar organic solvents, such as DMF, THF and methanol, but none of the cationic Pcs was water soluble; they remained aggregated in water, even upon sonication. To compare how the samples self-assemble into aggregate structures, AFM studies were accomplished using tapping-mode for samples prepared on mica surfaces. Topography views are shown in Figure 1 for samples of Pcs 6a, 2b, and 16a. Considerable differences are apparent for the heights and surface coverage of the samples. The largest aggregates were revealed for the non-pegylated Pc 6a, with an average height of 9.6 ± 0.5 nm (mean ± standard error, n = 93). Most of the clusters (70%) ranged from 8 to 14 nm in height. The smallest clusters were observed for Pc 16a containing a longer PEG chain than 2b, measuring 1.0 ± 0.15 nm (n = 52). The average size of surface deposits for Pc 2b measured 1.1 ± 0.1 nm, with most of the clusters measuring 0.6 to 1.2 nm in height (77%, n = 227). The sizes were measured using height information obtained from individual cursor profiles within the images. The lateral dimensions of surface features depend closely on the AFM probe geometry and are not as reliable for estimating sizes. Comparing the samples using a t-test, the mean values for 16a and 2b indicate that the surface structures are essentially the same height. However, the size of the aggregates of Pc 6a is significantly larger than those of either Pcs 2b or 16a. The sizes of aggregates follow the trend: Pc 6a >> Pc 2b > Pc 16a.


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)

Side-by-side comparison of sample aggregation on surfaces of mica(0001). Topography images of Pcs (A) 6a, (B) 2b, and (C) 16a, with corresponding cursor profiles. The frame sizes are 2 × 2 µm2, acquired in ambient air using tapping-mode AFM.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475216&req=5

Figure 1: Side-by-side comparison of sample aggregation on surfaces of mica(0001). Topography images of Pcs (A) 6a, (B) 2b, and (C) 16a, with corresponding cursor profiles. The frame sizes are 2 × 2 µm2, acquired in ambient air using tapping-mode AFM.
Mentions: All di-cationic ZnPcs 4a,b, 6a,b, 9a,b, 11a,b, and 16a,b are soluble in polar organic solvents, such as DMF, THF and methanol, but none of the cationic Pcs was water soluble; they remained aggregated in water, even upon sonication. To compare how the samples self-assemble into aggregate structures, AFM studies were accomplished using tapping-mode for samples prepared on mica surfaces. Topography views are shown in Figure 1 for samples of Pcs 6a, 2b, and 16a. Considerable differences are apparent for the heights and surface coverage of the samples. The largest aggregates were revealed for the non-pegylated Pc 6a, with an average height of 9.6 ± 0.5 nm (mean ± standard error, n = 93). Most of the clusters (70%) ranged from 8 to 14 nm in height. The smallest clusters were observed for Pc 16a containing a longer PEG chain than 2b, measuring 1.0 ± 0.15 nm (n = 52). The average size of surface deposits for Pc 2b measured 1.1 ± 0.1 nm, with most of the clusters measuring 0.6 to 1.2 nm in height (77%, n = 227). The sizes were measured using height information obtained from individual cursor profiles within the images. The lateral dimensions of surface features depend closely on the AFM probe geometry and are not as reliable for estimating sizes. Comparing the samples using a t-test, the mean values for 16a and 2b indicate that the surface structures are essentially the same height. However, the size of the aggregates of Pc 6a is significantly larger than those of either Pcs 2b or 16a. The sizes of aggregates follow the trend: Pc 6a >> Pc 2b > Pc 16a.

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