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Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics.

Josefsen LB, Boyle RW - Theranostics (2012)

Bottom Line: Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types.Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms.The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, The University Of Hull, Kingston-Upon-Hull, HU6 7RX, U.K.

ABSTRACT
Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types. Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms. The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review.

No MeSH data available.


Related in: MedlinePlus

Unsubstituted ZnPC.
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Figure 17: Unsubstituted ZnPC.

Mentions: Serum albumin is the most abundant protein in humans - it is approximately ten times the total concentration of all other lipoproteins found in the blood 3, 6, 14, 24, 25, 135, 136. Over 60% of the protein is found in interstitial fluid - fluid which surrounds cells and acts as a medium to provide nutrients to and remove waste products from the cells. Serum albumin is unique in its ability to bind, covalently or reversibly, with a large number of ligands with a high degree of affinity. It has been reported that photosensitisers possessing a high affinity for serum albumins could be efficient pdt agents; tumour cells have a higher rate of serum albumin turnover due to their increased metabolism and rate of proliferation 135. One of the first studies into albumin binding with respect to targeted-pdt centred on the non-covalent binding (NCB) of an unsubstituted ZnPC (figure 17) to bovine serum albumin (BSA). Results were promising - tumour regression was observed (EMT-6 mouse mammary tumours on Balb/c mice and T380 human colon carcinomas on nude mice) with no hepatic toxicity. However, further tests indicated that, post-intravenous administration, the ZnPC redistributed towards the high density lipoprotein (HDL) fraction of the serum 135. To circumvent this behaviour research concentrated on the covalent binding of photosensitisers to albumin 135. Physically-modified albumin is targeted by scavenger receptors that are expressed in high concentrations on macrophages. The macrophages bind a broad range of different ligands and transport them to subcellular compartments; oxidised low density lipoprotein (LDL) and maleylated BSA readily bind to macrophages while native proteins do not. Estimates suggest that in several cancers greater than half of a tumours mass is of macrophage lineage giving the potential for targeting photosensitisers to the tumour by targeting macrophages. Reports suggest tumour-associated macrophages accumulate greater concentrations of photosensitiser than neighbouring tumour cells with a 9-fold increase observed for porphyrins. Results for other photosensitisers (porphyrins, PCs, chlorins) conjugated to albumin (BSA and maleylated BSA) have shown promise against a range of tumour cell-lines (human colon carcinoma HT29 tumour cells and J774 macrophage cell line from Balb/c mouse tumour cells). Albumin-conjugated photosensitisers have also shown promise in the treatment of arterial occlusion (inhibition of intimal hyperplasia and decreased restenosis post-initial disease therapy) and as agents to induce photodynamic tissue adhesion via tissue soldering 119, 135-141.


Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics.

Josefsen LB, Boyle RW - Theranostics (2012)

Unsubstituted ZnPC.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475217&req=5

Figure 17: Unsubstituted ZnPC.
Mentions: Serum albumin is the most abundant protein in humans - it is approximately ten times the total concentration of all other lipoproteins found in the blood 3, 6, 14, 24, 25, 135, 136. Over 60% of the protein is found in interstitial fluid - fluid which surrounds cells and acts as a medium to provide nutrients to and remove waste products from the cells. Serum albumin is unique in its ability to bind, covalently or reversibly, with a large number of ligands with a high degree of affinity. It has been reported that photosensitisers possessing a high affinity for serum albumins could be efficient pdt agents; tumour cells have a higher rate of serum albumin turnover due to their increased metabolism and rate of proliferation 135. One of the first studies into albumin binding with respect to targeted-pdt centred on the non-covalent binding (NCB) of an unsubstituted ZnPC (figure 17) to bovine serum albumin (BSA). Results were promising - tumour regression was observed (EMT-6 mouse mammary tumours on Balb/c mice and T380 human colon carcinomas on nude mice) with no hepatic toxicity. However, further tests indicated that, post-intravenous administration, the ZnPC redistributed towards the high density lipoprotein (HDL) fraction of the serum 135. To circumvent this behaviour research concentrated on the covalent binding of photosensitisers to albumin 135. Physically-modified albumin is targeted by scavenger receptors that are expressed in high concentrations on macrophages. The macrophages bind a broad range of different ligands and transport them to subcellular compartments; oxidised low density lipoprotein (LDL) and maleylated BSA readily bind to macrophages while native proteins do not. Estimates suggest that in several cancers greater than half of a tumours mass is of macrophage lineage giving the potential for targeting photosensitisers to the tumour by targeting macrophages. Reports suggest tumour-associated macrophages accumulate greater concentrations of photosensitiser than neighbouring tumour cells with a 9-fold increase observed for porphyrins. Results for other photosensitisers (porphyrins, PCs, chlorins) conjugated to albumin (BSA and maleylated BSA) have shown promise against a range of tumour cell-lines (human colon carcinoma HT29 tumour cells and J774 macrophage cell line from Balb/c mouse tumour cells). Albumin-conjugated photosensitisers have also shown promise in the treatment of arterial occlusion (inhibition of intimal hyperplasia and decreased restenosis post-initial disease therapy) and as agents to induce photodynamic tissue adhesion via tissue soldering 119, 135-141.

Bottom Line: Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types.Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms.The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, The University Of Hull, Kingston-Upon-Hull, HU6 7RX, U.K.

ABSTRACT
Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types. Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms. The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review.

No MeSH data available.


Related in: MedlinePlus