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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

Zinc-Metallated Porphyrazine.
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Figure 13: Zinc-Metallated Porphyrazine.

Mentions: The prodrug 5-aminolaevulinic acid (δ-aminolaevulinic acid, ALA, marketed as Levulan®) generates the photosensitiser protoporphyrin IX (PPIX), via the haem biosynthetic pathway, when internalised by cells and is used in the imaging and treatment of superficial tumours. It has also been used as a topical treatment for dermatological conditions (psoriasis, Bowen's disease and acne). ALA derivatives are used in the clinic for imaging and treatment of basal cell carcinomas and other skin lesions (Metvix®, a methyl ester derivative), Benvix® (a benzyl ester derivative) and Hexvix® (a hexyl derivative) have also been employed in the treatment of gastrointestinal cancers and in the diagnosis of bladder cancer 4, 7, 14, 24, 25, 29, 50, 71. The ability of small molecule ALA derivatives to penetrate the skin selectively where tumours are present and both fluoresce and photosensitise the tumours via in situ production of PPIX makes them ideal theranostic agents. A benzoporphyrin derivative, monoacid ring A (BPD-MA, trade name Visudyne®, Verteporfin® for injection) was developed and approved for use in wet age-related macular degeneration (wAMD) and cutaneous non-melanoma skin cancer. The success of Verteporfin® could be attributed to the red-shifted and intensified long-wavelength absorption maxima (approximately 690nm) - light can penetrate 50% deeper into the skin at this wavelength in comparison to Photofrin® 4, 7, 14, 25, 27, 29, 72-74. Tin etiopurpurin (Purlytin®, figure 12), a chlorin-based photosensitiser, is a derivative of the porphyrin chromophore with a reduced exocyclic double bond and an intensified long-wavelength absorption - the tin atom chelated in the central cavity further increases the red shift (20-30nm) of the drug (650-680nm). Purlytin® has been approved (USA) for cutaneous metastatic breast cancer, Kaposi's sarcoma in patients with AIDS and for the treatment of psoriasis and restenosis 4, 7, 14, 25, 27, 29, 50, 75, 76. Tetra(m-hydroxyphenyl)chlorin (mTHPC, Foscan®/Temoporfin®, USA and Europe) has been evaluated for use in the pdt of head and neck cancers as well as gastric and pancreatic cancers, hyperplasia, field sterilisation after cancer surgery and for the control of antibiotic-resistant bacteria (USA, Europe and the Far East). Advantages of Foscan® are the low drug and light doses required to achieve suitable photodynamic responses - Foscan® is approximately 100 times more photoactive than Photofrin®, although patients can remain photosensitive for up to 20 days (the length of photosensitivity varies between the second-generation photosensitisers from 1-2 days (Verteporfin) to up to 2 weeks (Purlytin) 4, 7, 14, 24, 25, 27, 29, 50, 71, 77, 78. First-generation photosensitisers can render patients photosensitive for 90 days. Lutetium texaphyrin (Lutex®/Lutrin®), an expanded porphyrin with a penta-aza core, exhibits strong absorption in the 730-770nm region of the EMS, a region where tissue transparency is optimal. Lutex® has been approved for the treatment of breast cancer and malignant melanomas (USA). Antrin®, a Lutex® derivative, has undergone trials for the prevention of restenosis, while Optrin®, a second derivative, has been in trials for the management of AMD 4, 7, 14, 24, 25, 29, 50, 76, 79-82. Texaphyrins have also been developed for use as radiosensitisers and chemosensitisers - a gadolinium complex has been investigated as a MRI contrast agent. 9-Acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene (ATMPn®, porphycenes are structural isomers of porphyrins), absorption maxima ~640nm has been evaluated against psoriasis vulgaris and superficial non-melanoma skin cancer (USA) 4, 7, 83-86. Zinc phthalocyanine (CGP55847) has undergone clinical trials against squamous cell carcinomas (SCC) of the upper aerodigestive tract (Canada) 4, 7, 24, 76, 87-93. A sulphonated aluminium PC derivative (Photosens®, Russia) entered clinical trials against skin, breast and lung malignancies and cancer of the gastrointestinal tract 4, 7, 24, 94-96. Sulphonation of the PC significantly increases PC solubility in polar solvents including water, circumventing the need for alternative delivery vehicles. A silicon PC complex (PC4) has been evaluated for the sterilisation of blood components (USA), and against breast, colon and ovarian cancers and gliomas 4, 7, 97-103. A drawback of metallo-PCs can be their tendency to aggregate in aqueous buffer (pH 7.4), leading to a decrease or total loss of their photochemical activity; detergents can limit this behaviour 7, 76. Tetraazaporphyrins, porphyrazine (PZ, figure 13) derivatives, have been evaluated against Chinese hamster lung fibroblast cells; the PZs that exhibited the greatest induction of dark toxicity include the metallated cationic complexes PdPZ+, CuPZ+, CdPZ+, MgPZ+, AlPZ+ and GaPZ+7, 76.


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

Josefsen LB, Boyle RW - Theranostics (2012)

Zinc-Metallated Porphyrazine.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 13: Zinc-Metallated Porphyrazine.
Mentions: The prodrug 5-aminolaevulinic acid (δ-aminolaevulinic acid, ALA, marketed as Levulan®) generates the photosensitiser protoporphyrin IX (PPIX), via the haem biosynthetic pathway, when internalised by cells and is used in the imaging and treatment of superficial tumours. It has also been used as a topical treatment for dermatological conditions (psoriasis, Bowen's disease and acne). ALA derivatives are used in the clinic for imaging and treatment of basal cell carcinomas and other skin lesions (Metvix®, a methyl ester derivative), Benvix® (a benzyl ester derivative) and Hexvix® (a hexyl derivative) have also been employed in the treatment of gastrointestinal cancers and in the diagnosis of bladder cancer 4, 7, 14, 24, 25, 29, 50, 71. The ability of small molecule ALA derivatives to penetrate the skin selectively where tumours are present and both fluoresce and photosensitise the tumours via in situ production of PPIX makes them ideal theranostic agents. A benzoporphyrin derivative, monoacid ring A (BPD-MA, trade name Visudyne®, Verteporfin® for injection) was developed and approved for use in wet age-related macular degeneration (wAMD) and cutaneous non-melanoma skin cancer. The success of Verteporfin® could be attributed to the red-shifted and intensified long-wavelength absorption maxima (approximately 690nm) - light can penetrate 50% deeper into the skin at this wavelength in comparison to Photofrin® 4, 7, 14, 25, 27, 29, 72-74. Tin etiopurpurin (Purlytin®, figure 12), a chlorin-based photosensitiser, is a derivative of the porphyrin chromophore with a reduced exocyclic double bond and an intensified long-wavelength absorption - the tin atom chelated in the central cavity further increases the red shift (20-30nm) of the drug (650-680nm). Purlytin® has been approved (USA) for cutaneous metastatic breast cancer, Kaposi's sarcoma in patients with AIDS and for the treatment of psoriasis and restenosis 4, 7, 14, 25, 27, 29, 50, 75, 76. Tetra(m-hydroxyphenyl)chlorin (mTHPC, Foscan®/Temoporfin®, USA and Europe) has been evaluated for use in the pdt of head and neck cancers as well as gastric and pancreatic cancers, hyperplasia, field sterilisation after cancer surgery and for the control of antibiotic-resistant bacteria (USA, Europe and the Far East). Advantages of Foscan® are the low drug and light doses required to achieve suitable photodynamic responses - Foscan® is approximately 100 times more photoactive than Photofrin®, although patients can remain photosensitive for up to 20 days (the length of photosensitivity varies between the second-generation photosensitisers from 1-2 days (Verteporfin) to up to 2 weeks (Purlytin) 4, 7, 14, 24, 25, 27, 29, 50, 71, 77, 78. First-generation photosensitisers can render patients photosensitive for 90 days. Lutetium texaphyrin (Lutex®/Lutrin®), an expanded porphyrin with a penta-aza core, exhibits strong absorption in the 730-770nm region of the EMS, a region where tissue transparency is optimal. Lutex® has been approved for the treatment of breast cancer and malignant melanomas (USA). Antrin®, a Lutex® derivative, has undergone trials for the prevention of restenosis, while Optrin®, a second derivative, has been in trials for the management of AMD 4, 7, 14, 24, 25, 29, 50, 76, 79-82. Texaphyrins have also been developed for use as radiosensitisers and chemosensitisers - a gadolinium complex has been investigated as a MRI contrast agent. 9-Acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene (ATMPn®, porphycenes are structural isomers of porphyrins), absorption maxima ~640nm has been evaluated against psoriasis vulgaris and superficial non-melanoma skin cancer (USA) 4, 7, 83-86. Zinc phthalocyanine (CGP55847) has undergone clinical trials against squamous cell carcinomas (SCC) of the upper aerodigestive tract (Canada) 4, 7, 24, 76, 87-93. A sulphonated aluminium PC derivative (Photosens®, Russia) entered clinical trials against skin, breast and lung malignancies and cancer of the gastrointestinal tract 4, 7, 24, 94-96. Sulphonation of the PC significantly increases PC solubility in polar solvents including water, circumventing the need for alternative delivery vehicles. A silicon PC complex (PC4) has been evaluated for the sterilisation of blood components (USA), and against breast, colon and ovarian cancers and gliomas 4, 7, 97-103. A drawback of metallo-PCs can be their tendency to aggregate in aqueous buffer (pH 7.4), leading to a decrease or total loss of their photochemical activity; detergents can limit this behaviour 7, 76. Tetraazaporphyrins, porphyrazine (PZ, figure 13) derivatives, have been evaluated against Chinese hamster lung fibroblast cells; the PZs that exhibited the greatest induction of dark toxicity include the metallated cationic complexes PdPZ+, CuPZ+, CdPZ+, MgPZ+, AlPZ+ and GaPZ+7, 76.

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