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1aa80d112a893196e4c08a4f402b6e323825a8af
in the 1980s, david dolphin, julia levy and
in the 1980s, david dolphin, julia levy and colleagues developed a novel photosensitizer, verteporfin. verteporfin, a porphyrin derivative, is activated at 690 nm, a much longer wavelength than photofrin. it has the property of preferential uptake by neovasculature. it has been widely tested for its use in treating ski...
wikipedia
03d9f88e87cd207b862267a53e4337c1d4f4d28e
photofrin had the disadvantages of prolonged patient photosensitivity
photofrin had the disadvantages of prolonged patient photosensitivity and a weak long-wavelength absorption (630 nm). this led to the development of second generation photosensitisers, including verteporfin (a benzoporphyrin derivative, also known as visudyne) and more recently, third generation targetable photosensiti...
wikipedia
d8f99150495386a7feeed31eee381a1fa8eb86c7
hpd, under the brand name photofrin, was the
hpd, under the brand name photofrin, was the first pdt agent approved for clinical use in 1993 to treat a form of bladder cancer in canada. over the next decade, both pdt and the use of hpd received international attention and greater clinical acceptance and led to the first pdt treatments approved by u.s. food and dru...
wikipedia
3c7c0916d23f994810f41a5cae93e66e7e2fe20a
john toth, product manager for cooper medical devices
john toth, product manager for cooper medical devices corp/cooper lasersonics, noticed the "photodynamic chemical effect" of the therapy and wrote the first white paper naming the therapy "photodynamic therapy" (pdt) with early clinical argon dye lasers circa 1981. the company set up 10 clinical sites in japan where th...
wikipedia
35229438b3a9d6a0dbb4cac7da8439a4b81e38ce
thomas dougherty and co-workers at roswell park comprehensive
thomas dougherty and co-workers at roswell park comprehensive cancer center in buffalo, new york, clinically tested pdt in 1978. they treated 113 cutaneous or subcutaneous malignant tumors with hpd and observed total or partial resolution of 111 tumors. dougherty helped expand clinical trials and formed the internation...
wikipedia
887b44ec89179ea1d1dff6e86e9b339c5628c931
photosensitizer haematoporphyrin derivative (hpd), was first characterised in
photosensitizer haematoporphyrin derivative (hpd), was first characterised in 1960 by lipson. lipson sought a diagnostic agent suitable for tumor detection. hpd allowed lipson to pioneer the use of endoscopes and hpd fluorescence. hpd is a porphyrin species derived from haematoporphyrin, porphyrins have long been consi...
wikipedia
755447e968b8fd9ba1ece70c3b9341299dc40837
in 1948 figge and co-workers showed on laboratory
in 1948 figge and co-workers showed on laboratory animals that porphyrins exhibit a preferential affinity to rapidly dividing cells, including malignant, embryonic and regenerative cells. they proposed that porphyrins could be used to treat cancer.
wikipedia
d9553e52c0dc3d9a7ff301ade9befbc6323ed414
in 1924 policard revealed the diagnostic capabilities of
in 1924 policard revealed the diagnostic capabilities of hematoporphyrin fluorescence when he observed that ultraviolet radiation excited red fluorescence in the sarcomas of laboratory rats. policard hypothesized that the fluorescence was associated with endogenous hematoporphyrin accumulation.
wikipedia
0caef4d752a6f8bd6bab79d6497d55a2930bbaec
von tappeiner and colleagues performed the first pdt
von tappeiner and colleagues performed the first pdt trial in patients with skin carcinoma using the photosensitizer, eosin. of six patients with a facial basal cell carcinoma, treated with a 1% eosin solution and long-term exposure either to sunlight or arc-lamp light, four patients showed total tumour resolution and ...
wikipedia
ee22e3f51aa223271fb4da6447ee330af6a3b01c
while studying the effects of acridine on paramecia
while studying the effects of acridine on paramecia cultures, oscar raab, a student of von tappeiner observed a toxic effect. fortuitously raab also observed that light was required to kill the paramecia. subsequent work in von tappeiner's laboratory showed that oxygen was essential for the 'photodynamic action' – a te...
wikipedia
ad0a5b1cee1716698492a1cc8db33e5599405ff4
the first evidence that agents, photosensitive synthetic dyes,
the first evidence that agents, photosensitive synthetic dyes, in combination with a light source and oxygen could have potential therapeutic effect was made at the turn of the 20th century in the laboratory of hermann von tappeiner in munich, germany. germany was leading the world in industrial dye synthesis at the ti...
wikipedia
3b857059b63b91397829bfbde86e1c9ef942b8dd
in 1913 another german scientist, meyer-betz, described the
in 1913 another german scientist, meyer-betz, described the major stumbling block of photodynamic therapy. after injecting himself with haematoporphyrin (hp, a photosensitiser), he swiftly experienced a general skin sensitivity upon exposure to sunlight—a recurrent problem with many photosensitisers.
wikipedia
5fe8b95f95e6ed707318895f7ee3d6736d04c9d0
in the late nineteenth century. finsen successfully demonstrated
in the late nineteenth century. finsen successfully demonstrated phototherapy by employing heat-filtered light from a carbon-arc lamp (the "finsen lamp") in the treatment of a tubercular condition of the skin known as lupus vulgaris, for which he won the 1903 nobel prize in physiology or medicine.
wikipedia
d7c142b232bc5b0fcd29ed08b22a20b3b02fd5de
photodynamic skin disinfection is effective at killing topical
photodynamic skin disinfection is effective at killing topical microbes, including drug-resistant bacteria, viruses, and fungi. photodynamic disinfection remains effective after repeat treatments, with no evidence of resistance formation. the method can effectively treat polymicrobial antibiotic resistant pseudomonas a...
wikipedia
7c6e89cf8b33e4b361d76e8ed31c7214492f19a0
compared to normal tissues, most types of cancers
compared to normal tissues, most types of cancers are especially active in both the uptake and accumulation of photosensitizers agents, which makes cancers especially vulnerable to pdt. since photosensitizers can also have a high affinity for vascular endothelial cells.
wikipedia
f7e7e6877c0f07b5a590f9c3f7c3d9c41b54a994
pdt is a minimally invasive treatment that is
pdt is a minimally invasive treatment that is used to treat many conditions including acne, psoriasis, age related macular degeneration, and several cancers such as skin, lung, brain, mesothelioma, bladder, bile-duct, esophageal, and head and neck cancers.
wikipedia
583fffcfa169c1ab5817a908c8cc834cfcecc8c4
when cells that have absorbed photosensitizers are exposed
when cells that have absorbed photosensitizers are exposed to a specific wavelength of light, the photosensitizer produces a form of oxygen, called an oxygen radical, that kills them. photodynamic therapy (pdt) may also damage blood vessels in the tumor, which prevents it from receiving the blood it needs to keep growi...
wikipedia
38e0e3cbcee0e680f379c696c3de17d20aa73946
the fda has approved photodynamic therapy to treat
the fda has approved photodynamic therapy to treat actinic keratosis, advanced cutaneous t-cell lymphoma, barrett esophagus, basal cell skin cancer, esophageal (throat) cancer, non-small cell lung cancer, and squamous cell skin cancer (stage 0). photodynamic therapy is also used to relieve symptoms of some cancers, inc...
wikipedia
18822580cf0e6ea49698adb3d6ac37cb4e28fcbe
pdt is currently in clinical trials as a
pdt is currently in clinical trials as a treatment for severe acne. initial results have shown for it to be effective as a treatment only for severe acne. a systematic review conducted in 2016 found that pdt is a "safe and effective method of treatment" for acne. the treatment may cause severe redness and moderate to s...
wikipedia
a2d9412199ebf3101e82fb09b83f9f122a0f13e9
photosensitizers can target viral and microbial species, including
photosensitizers can target viral and microbial species, including hiv and mrsa. using pdt, pathogens present in samples of blood and bone marrow can be decontaminated before the samples are used further for transfusions or transplants. pdt can also eradicate a wide variety of pathogens of the skin and of the oral cavi...
wikipedia
be4e2b8939f3a6904ae8d74bb13bd6617fabc27f
to achieve selective target cell destruction, while protecting
to achieve selective target cell destruction, while protecting normal tissues, either the photosensitizer can be applied locally to the target area, or targets can be locally illuminated. skin conditions, including acne, psoriasis and also skin cancers, can be treated topically and locally illuminated. for internal tis...
wikipedia
172addde539472a1ce69abf2403f1fd66ed76d76
the +2 charged diamagnetic species appeared to exhibit
the +2 charged diamagnetic species appeared to exhibit a direct relationship between their fluorescence quantum yields, excited state lifetimes, rate of isc and the atomic number of the metal ion. the greatest diamagnetic isc rate was observed for lu-tex; a result ascribed to the heavy atom effect. the heavy atom effec...
wikipedia
efbd147a97a3d44c4dcd9de6fbdd0c39c3d5ebec
various diamagnetic and paramagnetic texaphyrins investigated have independent
various diamagnetic and paramagnetic texaphyrins investigated have independent photophysical behaviour with respect to a complex's magnetism. the diamagnetic complexes were characterised by relatively high fluorescence quantum yields, excited-singlet and triplet lifetimes and singlet oxygen quantum yields; in distinct ...
wikipedia
b9e73ed37ba83a5bd351816db118e53dcce058e5
paramagnetic metallo-texaphyrins displayed rapid isc. triplet lifetimes were
paramagnetic metallo-texaphyrins displayed rapid isc. triplet lifetimes were strongly affected by the choice of metal ion. the diamagnetic ions (y, in and lu) displayed triplet lifetimes ranging from 187, 126 and 35 μ s, respectively. comparable lifetimes for the paramagnetic species (eu-tex 6.98 μ s, gd-tex 1.11, tb-t...
wikipedia
88dffb7bed7cbe7de4699100237d8533ad6f57e7
an extensive study of metallated texaphyrins focused on
an extensive study of metallated texaphyrins focused on the lanthanide (iii) metal ions, y, in, lu, cd, nd, sm, eu, gd, tb, dy, ho, er, tm and yb found that when diamagnetic lu (iii) was complexed to texaphyrin, an effective photosensitiser (lutex) was generated. however, using the paramagnetic gd (iii) ion for the lu ...
wikipedia
aeef43ad3b8f7eab0d4bc7af31a92e62a79df481
in porphyrin systems, the zinc ion (zn) appears
in porphyrin systems, the zinc ion (zn) appears to hinder the photodynamic activity of the compound. by contrast, in the higher/expanded π -systems, zinc-chelated dyes form complexes with good to high results.
wikipedia
a4e351381081f5a15ad837e799e813dd1d7e1f5b
work with zinc nc with various amido substituents
work with zinc nc with various amido substituents revealed that the best phototherapeutic response (lewis lung carcinoma in mice) with a tetrabenzamido analogue. complexes of silicon (iv) ncs with two axial ligands in anticipation the ligands minimise aggregation. disubstituted analogues as potential photodynamic agent...
wikipedia
b65e807d524d82877f65c0f9aa54fbf1eb259dc6
aluminium (al) has been successfully coordinated to m-nsbp.
aluminium (al) has been successfully coordinated to m-nsbp. the resulting complex showed photodynamic activity against emt-6 tumour-bearing balb/c mice (disulphonated analogue demonstrated greater photoactivity than the mono-derivative).
wikipedia
1772c05b67f5d531996ce77c4bea3d797b842211
pcs properties are strongly influenced by the central
pcs properties are strongly influenced by the central metal ion. co-ordination of transition metal ions gives metallo-complexes with short triplet lifetimes (nanosecond range), resulting in different triplet quantum yields and lifetimes (with respect to the non-metallated analogues). diamagnetic metals such as zinc, al...
wikipedia
a257e038688ebb6def531255ea35844fa8850bb4
copper octaethylbenzochlorin demonstrated greater photoactivity towards leukemia cells
copper octaethylbenzochlorin demonstrated greater photoactivity towards leukemia cells in vitro and a rat bladder tumour model. it may derive from interactions between the cationic iminium group and biomolecules. such interactions may allow electron-transfer reactions to take place via the short-lived excited singlet s...
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b3cff1cde63c12f3b725ea044f5fee6a9a55a91a
sulphonated benzochlorin derivatives demonstrated a reduced phototherapeutic response
sulphonated benzochlorin derivatives demonstrated a reduced phototherapeutic response against murine leukemia l1210 cells in vitro and transplanted urothelial cell carcinoma in rats, whereas the tin (iv) metallated benzochlorins exhibited an increased photodynamic effect in the same tumour model.
wikipedia
d2d059c63d647c323c1c76d3e1007db2107df7eb
a zinc-metallated seco - porphyrazine has a high
a zinc-metallated seco - porphyrazine has a high quantum singlet oxygen yield (ΦΔ 0.74). this expanded porphyrin-like photosensitiser has shown the best singlet oxygen photosensitising ability of any of the reported seco- porphyrazines. platinum and palladium derivatives have been synthesised with singlet oxygen quantu...
wikipedia
b0c3aa404c7d0263cad5a4a1602ee1eb9e3611ab
the cadmium-texaphyrin derivative has shown in vitro photodynamic
the cadmium-texaphyrin derivative has shown in vitro photodynamic activity against human leukemia cells and gram positive (staphylococcus) and gram negative (escherichia coli) bacteria. although follow-up studies have been limited with this photosensitiser due to the toxicity of the complexed cadmium ion.
wikipedia
f3ad4ea1d9fe7dfcb7842973eb9cc905c944f7c0
diamagnetic metallo-texaphyrins have shown photophysical properties; high triplet
diamagnetic metallo-texaphyrins have shown photophysical properties; high triplet quantum yields and efficient generation of singlet oxygen. in particular, the zinc and cadmium derivatives display triplet quantum yields close to unity. in contrast, the paramagnetic metallo-texaphyrins, mn-tex, sm-tex and eu-tex, have u...
wikipedia
cfd42c604d37036e3680184b42db898b6bd063b4
many metallated paramagnetic texaphyrin species exhibit triplet-state lifetimes
many metallated paramagnetic texaphyrin species exhibit triplet-state lifetimes in the nanosecond range. these results are mirrored by metallated pcs. pcs metallated with diamagnetic ions, such as zn, al and ga, generally yield photosensitisers with desirable quantum yields and lifetimes (Φt 0.56, 0.50 and 0.34 and τ t...
wikipedia
d05b653a26831b4b405c6cbbb4fc9d82f30a291e
certain heavy metals are known to enhance inter-system
certain heavy metals are known to enhance inter-system crossing (isc). generally, diamagnetic metals promote isc and have a long triplet lifetime. in contrast, paramagnetic species deactivate excited states, reducing the excited-state lifetime and preventing photochemical reactions. however, exceptions to this generali...
wikipedia
43629519561de5e35cb3c7ad6a3fee8acb2a25a4
the central metal ion, bound by a number
the central metal ion, bound by a number of photosensitisers, strongly influences the photophysical properties of the photosensitiser. chelation of paramagnetic metals to a pc chromophore appears to shorten triplet lifetimes (down to nanosecond range), generating variations in the triplet quantum yield and triplet life...
wikipedia
9f580b34c1df04eb3528754efde5db183d65e9a3
the metal ion does not confer definite photoactivity
the metal ion does not confer definite photoactivity on the complex. copper (ii), cobalt (ii), iron (ii) and zinc (ii) complexes of hp are all photoinactive in contrast to metal-free porphyrins. however, texaphyrin and pc photosensitisers do not contain metals; only the metallo-complexes have demonstrated efficient pho...
wikipedia
f92add8fda0878e59746c5ea156d67c3daa45145
various metals form into complexes with photosensitiser macrocycles.
various metals form into complexes with photosensitiser macrocycles. multiple second generation photosensitisers contain a chelated central metal ion. the main candidates are transition metals, although photosensitisers co-ordinated to group 13 (al, alpcs) and group 14 (si, sinc and sn, snet) metals have been synthesis...
wikipedia
fe90e8b6cb67c5a828a04e7278991c37c310eeae
alternate delivery strategies range from the use of
alternate delivery strategies range from the use of oil-in-water (o/w) emulsions to carrier vehicles such as liposomes and nanoparticles. although these systems may increase therapeutic effects, the carrier system may inadvertently decrease the "observed" singlet oxygen quantum yield (ΦΔ): the singlet oxygen generated ...
wikipedia
45e3670176944f8e6eaa4ad4a5bf7e1bc3edb726
the hydrophilic sulphonated porphyrins and pcs (alporphyrin and
the hydrophilic sulphonated porphyrins and pcs (alporphyrin and alpc) compounds were tested for photodynamic activity. the disulphonated analogues (with adjacent substituted sulphonated groups) exhibited greater photodynamic activity than their di-(symmetrical), mono-, tri- and tetra-sulphonated counterparts; tumour ac...
wikipedia
31dc4fcd17d4aa35c46dd2d7c2ff1e7b17bbeac7
another metallo-porphyrin complex, the iron chelate, is more
another metallo-porphyrin complex, the iron chelate, is more photoactive (towards hiv and simian immunodeficiency virus in mt-4 cells) than the manganese complexes; the zinc derivative is photoinactive.
wikipedia
e28fa40f1a94a08109cefe89638a7594b26ec74d
water-soluble cationic porphyrins bearing nitrophenyl, aminophenyl, hydroxyphenyl and/or
water-soluble cationic porphyrins bearing nitrophenyl, aminophenyl, hydroxyphenyl and/or pyridiniumyl functional groups exhibit varying cytotoxicity to cancer cells in vitro, depending on the nature of the metal ion (mn, fe, zn, ni) and on the number and type of functional groups. the manganese pyridiniumyl derivative ...
wikipedia
fb1eb4a3cba84bcfe9ce4ed1041590d2b64587d7
silicon naphthalocyanine attached to copolymer peg-pcl (poly(ethylene glycol)-
silicon naphthalocyanine attached to copolymer peg-pcl (poly(ethylene glycol)- block -poly(ε-caprolactone)) accumulates selectively in cancer cells and reaches a maximum concentration after about one day. the compound provides real time near-infrared (nir) fluorescence imaging with an extinction coefficient of 2.8 × 10...
wikipedia
adc6595766dc15693c5f9029ff5ed2ea4a367f6a
however, problems associated with nc photosensitisers include lower
however, problems associated with nc photosensitisers include lower stability, as they decompose in the presence of light and oxygen. metallo-ncs, which lack axial ligands, have a tendency to form h-aggregates in solution. these aggregates are photoinactive, thus compromising the photodynamic efficacy of ncs.
wikipedia
054f19290de189b82873a76ef4a66063098fc057
naphthalocyanines (ncs) are an extended pc derivative. they
naphthalocyanines (ncs) are an extended pc derivative. they have an additional benzene ring attached to each isoindole sub-unit on the periphery of the pc structure. subsequently, ncs absorb strongly at even longer wavelengths (approximately 740–780 nm) than pcs (670–780 nm). this absorption in the near infrared region...
wikipedia
302df7aba4a23e61a98043f3176530cec50f486a
metallated cationic porphyrazines (pz), including pdpz, cupz, cdpz,
metallated cationic porphyrazines (pz), including pdpz, cupz, cdpz, mgpz, alpz and gapz, have been tested in vitro on v-79 (chinese hamster lung fibroblast) cells. these photosensitisers display substantial dark toxicity.
wikipedia
d33b39117fde845b04c3cbc2c2f8597b61462777
a shortcoming of many of the metallo-pcs is
a shortcoming of many of the metallo-pcs is their tendency to aggregate in aqueous buffer (ph 7.4), resulting in a decrease, or total loss, of their photochemical activity. this behaviour can be minimised in the presence of detergents.
wikipedia
88b9154d8f7619f1831b4330b7d94a23bb752a6f
a sulphonated aluminium pc derivative (photosense) has entered
a sulphonated aluminium pc derivative (photosense) has entered clinical trials (russia) against skin, breast and lung malignancies and cancer of the gastrointestinal tract. sulphonation significantly increases pc solubility in polar solvents including water, circumventing the need for alternative delivery vehicles.
wikipedia
2515cef62fcda4faf7fb0b076bbc1eb84ee849c8
a liposomal formulation of zinc phthalocyanine (cgp55847) has
a liposomal formulation of zinc phthalocyanine (cgp55847) has undergone clinical trials (phase i/ii, switzerland) against squamous cell carcinomas of the upper aerodigestive tract. phthalocyanines (pcs) are related to tetra-aza porphyrins. instead of four bridging carbon atoms at the meso- positions, as for the porphyr...
wikipedia
bdf414b0306594f5d73be1217c4ab79ca0781863
9-acetoxy-2,7,12,17-tetrakis-(β -methoxyethyl)-porphycene has been evaluated as an agent
9-acetoxy-2,7,12,17-tetrakis-(β -methoxyethyl)-porphycene has been evaluated as an agent for dermatological applications against psoriasis vulgaris and superficial non-melanoma skin cancer.
wikipedia
53696e1c97a00d7176a93383477461ed32ecdfcd
texaphyrins also have potential as radiosensitisers (xcytrin) and
texaphyrins also have potential as radiosensitisers (xcytrin) and chemosensitisers. xcytrin, a gadolinium texaphyrin (motexafin gadolinium), has been evaluated in phase iii clinical trials against brain metastases and phase i clinical trials for primary brain tumours.
wikipedia
1e06191ff146ba2139edd475f3891c1eee4a3261
a lutex derivative, antrin, has undergone phase i
a lutex derivative, antrin, has undergone phase i clinical trials for the prevention of restenosis of vessels after cardiac angioplasty by photoinactivating foam cells that accumulate within arteriolar plaques. a second lutex derivative, optrin, is in phase i trials for amd.
wikipedia
2bb160371e8e1d2ca3c095e8b5ee2ac1cc98c304
lutetium texaphyrin, marketed under the trade name lutex
lutetium texaphyrin, marketed under the trade name lutex and lutrin, is a large porphyrin-like molecule. texaphyrins are expanded porphyrins that have a penta-aza core. it offers strong absorption in the 730–770 nm region. tissue transparency is optimal in this range. as a result, lutex-based pdt can (potentially) be c...
wikipedia
8d08f3c1e5b920e999dbda4243dc29a43f3708d7
tetra(m -hydroxyphenyl)chlorin (m thpc) is in clinical trials
tetra(m -hydroxyphenyl)chlorin (m thpc) is in clinical trials for head and neck cancers under the trade name foscan. it has also been investigated in clinical trials for gastric and pancreatic cancers, hyperplasia, field sterilisation after cancer surgery and for the control of antibiotic-resistant bacteria.
wikipedia
5f559414dd0cdca57ec1b8f0f3c19959768e17ed
purlytin has a tin atom chelated in its
purlytin has a tin atom chelated in its central cavity that causes a red-shift of approximately 20–30 nm (with respect to photofrin and non-metallated etiopurpurin, λ max.snet2 = 650 nm). purlytin has been reported to localise in skin and produce a photoreaction 7–14 days post-administration.
wikipedia
a24f735ab8bd893563b4ac8c5ef7dbf8c9a30a74
chlorins are distinguished from the parent porphyrins by
chlorins are distinguished from the parent porphyrins by a reduced exocyclic double bond, decreasing the symmetry of the conjugated macrocycle. this leads to increased absorption in the long-wavelength portion of the visible region of the electromagnetic spectrum (650–680 nm). purlytin is a purpurin; a degradation prod...
wikipedia
7de53037262ff30dbe27a8fe470458a94e8fb12d
chlorin photosensitiser tin etiopurpurin is marketed as purlytin.
chlorin photosensitiser tin etiopurpurin is marketed as purlytin. purlytin has undergone phase ii clinical trials for cutaneous metastatic breast cancer and kaposi's sarcoma in patients with aids (acquired immunodeficiency syndrome). purlytin has been used successfully to treat the non-malignant conditions psoriasis an...
wikipedia
4ef106fc3c98213bc982d31923d079c0c1e3ff4c
verteporfin has further advantages over the first generation
verteporfin has further advantages over the first generation sensitiser photofrin. it is rapidly absorbed by the tumour (optimal tumour-normal tissue ratio 30–150 minutes post-intravenous injection) and is rapidly cleared from the body, minimising patient photosensitivity (1–2 days).
wikipedia
67c2ce7ad7a9283a84cf3eb94f672f7fd42616a5
the chromophore of bpd-ma has a red-shifted and
the chromophore of bpd-ma has a red-shifted and intensified long-wavelength absorption maxima at approximately 690 nm. tissue penetration by light at this wavelength is 50% greater than that achieved for photofrin (λ max. = 630 nm).
wikipedia
c7d6eb565b9f7f648913dcb503c8f9d94f15d5dd
benzoporphyrin derivative monoacid ring a (bpd-ma), marketed as
benzoporphyrin derivative monoacid ring a (bpd-ma), marketed as visudyne (verteporfin, for injection), has been approved by health authorities in multiple jurisdictions, including us fda, for the treatment of wet amd beginning in 1999. it has also undergone phase iii clinical trials (usa) for the treatment of cutaneous...
wikipedia
a240ce59187a9542916105ec066246f08405faba
esterified ala derivatives with improved bioavailability have been
esterified ala derivatives with improved bioavailability have been examined. a methyl ala ester (metvix) is now available for basal cell carcinoma and other skin lesions. benzyl (benvix) and hexyl ester (hexvix) derivatives are used for gastrointestinal cancers and for the diagnosis of bladder cancer.
wikipedia
ace116e13d215de264b9142a50e4449c1cceb085
ala accumulates more rapidly in comparison to other
ala accumulates more rapidly in comparison to other intravenously administered sensitisers. typical peak tumour accumulation levels post-administration for ppix are usually achieved within several hours; other (intravenous) photosensitisers may take up to 96 hours to reach peak levels. ala is also excreted more rapidly...
wikipedia
8e46680ac49b5d0dfe22c86547f1bd05bd36765e
ala, marketed as levulan, has shown promise in
ala, marketed as levulan, has shown promise in photodynamic therapy (tumours) via both intravenous and oral administration, as well as through topical administration in the treatment of malignant and non-malignant dermatological conditions, including psoriasis, bowen's disease and hirsutism (phase ii/iii clinical trial...
wikipedia
504fe315790f0e592c6bd63cbf49898f6ff2483e
the haem molecule is synthesised from glycine and
the haem molecule is synthesised from glycine and succinyl coenzyme a (succinyl coa). the rate-limiting step in the biosynthesis pathway is controlled by a tight (negative) feedback mechanism in which the concentration of haem regulates the production of ala. however, this controlled feedback can be by-passed by artifi...
wikipedia
18b1ec54ff366b0a1d6db7aafd5f6d02e7513722
haem is synthesised in every energy-producing cell in
haem is synthesised in every energy-producing cell in the body and is a key structural component of haemoglobin, myoglobin and other haemproteins. the immediate precursor to haem is protoporphyrin ix (ppix), an effective photosensitiser. haem itself is not a photosensitiser, due to the coordination of a paramagnetic io...
wikipedia
15dd5b32ac49c639b05a04568dba0c3abd98b5e5
disadvantages associated with first generation photosensitisers include skin
disadvantages associated with first generation photosensitisers include skin sensitivity and absorption at 630 nm permitted some therapeutic use, but they markedly limited application to the wider field of disease. second generation photosensitisers were key to the development of photodynamic therapy.
wikipedia
160109f645b5d4941580287ecc883ca6b8332fc6
pdt was first discovered more than a century
pdt was first discovered more than a century ago in germany, it was not until thomas dougherty's when pdt became more mainstream. prior to dr. dougherty, researchers had ways of using light-sensitive compounds to treat disease. dougherty successfully treated cancer with pdt in preclinical models in 1975. three years la...
wikipedia
2eb56c796951ca3da748ead7d50004bab470d47a
porfimer sodium is a drug used to treat
porfimer sodium is a drug used to treat some types of cancer. when absorbed by cancer cells and exposed to light, porfimer sodium becomes active and kills the cancer cells. it is a type of photodynamic therapy (pdt) agent and also called photofrin.
wikipedia
8f4bfcf8dd3829a234c15bd255857ae0479ac1d4
the soret band arises from a strong electronic
the soret band arises from a strong electronic transition from the ground state to the second excited singlet state (s0 → s2); whereas the q band is a result of a weak transition to the first excited singlet state (s0 → s1). the dissipation of energy via internal conversion (ic) is so rapid that fluorescence is only ob...
wikipedia
43d5014f67e3b41d41de5a5d362a31dac4bbe7de
porphyrin's highly conjugated skeleton produces a characteristic ultra-violet
porphyrin's highly conjugated skeleton produces a characteristic ultra-violet visible (uv-vis) spectrum. the spectrum typically consists of an intense, narrow absorption band (ε > 200000 l⋅mol−1 cm−1) at around 400 nm, known as the soret band or b band, followed by four longer wavelength (450–700 nm), weaker absorption...
wikipedia
1805ee4693122f35190e93eeade9c9fd8d53b841
the inner two protons of a free-base porphyrin
the inner two protons of a free-base porphyrin can be removed by strong bases such as alkoxides, forming a dianionic molecule; conversely, the inner two pyrrolenine nitrogens can be protonated with acids such as trifluoroacetic acid affording a dicationic intermediate. the tetradentate anionic species can readily form ...
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porphyrins are a group of naturally occurring and
porphyrins are a group of naturally occurring and intensely coloured compounds, whose name is drawn from the greek word porphura, or purple. these molecules perform biologically important roles, including oxygen transport and photosynthesis and have applications in fields ranging from fluorescent imaging to medicine. p...
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the major difference between photosensitizers is the parts
the major difference between photosensitizers is the parts of the cell that they target. unlike in radiation therapy, where damage is done by targeting cell dna, most photosensitizers target other cell structures. for example, mthpc localizes in the nuclear envelope. in contrast, ala localizes in the mitochondria and m...
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photosensitizers commercially available for clinical use include allumera,
photosensitizers commercially available for clinical use include allumera, photofrin, visudyne, levulan, foscan, metvix, hexvix, cysview and laserphyrin, with others in development, e.g. antrin, photochlor, photosens, photrex, lumacan, cevira, visonac, bf-200 ala, amphinex and azadipyrromethenes.
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c5e9fba97b801641cbd4686c4bb54089fa502549
many photosensitizers for pdt exist. they divide into
many photosensitizers for pdt exist. they divide into porphyrins, chlorins and dyes. examples include aminolevulinic acid (ala), silicon phthalocyanine pc 4, m-tetrahydroxyphenylchlorin (mthpc) and mono-l-aspartyl chlorin e6 (npe6).
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6d98c2f13002c7ea0541042ff168b92a3b8e4fa2
the efficiency of type-ii processes is dependent upon
the efficiency of type-ii processes is dependent upon the triplet state lifetime τ t and the triplet quantum yield (Φt) of the photosensitiser. both of these parameters have been implicated in phototherapeutic effectiveness; further supporting the distinction between type-i and type-ii mechanisms. however, the success ...
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62334e1f89b0aa094417ffb5fe1b5b5023fd63cf
it is probable that in the presence of
it is probable that in the presence of molecular oxygen and as a direct result of the photoirradiation of the photosensitiser molecule, both type-i and ii pathways play a pivotal role in disrupting cellular mechanisms and cellular structure. nevertheless, considerable evidence suggests that the type-ii photo-oxygenatio...
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b5f43ef9610ce7d4583e7b226f18e1a66c886b47
it is possible that (over a 6 μs
it is possible that (over a 6 μs period) singlet oxygen can diffuse up to approximately 300 nm in vivo. singlet oxygen can theoretically only interact with proximal molecules and structures within this radius. ros initiate reactions with many biomolecules, including amino acid residues in proteins, such as tryptophan; ...
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when the excited photosensitiser collides with molecular oxygen,
when the excited photosensitiser collides with molecular oxygen, a process of triplet-triplet annihilation takes place (3psen* → 1psen and o → o). this inverts the spin of one oxygen molecule's (o) outermost antibonding electrons, generating two forms of singlet oxygen (Δ and Σ), while simultaneously depopulating the p...
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357fd3bf9cdef95dc654232fc9aac4d282a888a0
type-ii processes involve the direct interaction of the
type-ii processes involve the direct interaction of the excited triplet state photosensitiser (3psen*) with ground state molecular oxygen (o, Σ); a spin allowed transition—the excited state photosensitiser and ground state molecular oxygen are of the same spin state (t).
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bbafad5bcea7e55f374baf7f3c1bb629e7b90eec
the type-i process (ii) involves the transfer of
the type-i process (ii) involves the transfer of a hydrogen atom (reduction) to the excited state photosensitiser (psen*). this generates free radicals capable of rapidly reacting with molecular oxygen and creating a complex mixture of reactive oxygen intermediates, including reactive peroxides.
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db6b71d886876d9803dc6ab7600024c6b1ba4151
type-i processes can be divided into type i(i)
type-i processes can be divided into type i(i) and type i(ii). type i (i) involves the transfer of an electron (oxidation) from a substrate molecule to the excited state photosensitiser (psen*), generating a photosensitiser radical anion (psen) and a substrate radical cation (subs). the majority of the radicals produce...
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de197f3ac16cd3641f449a61ff5d0cf2270cb971
excited triplet-state photosensitisers can react via type-i and
excited triplet-state photosensitisers can react via type-i and type-ii processes. type-i processes can involve the excited singlet or triplet photosensitiser (1psen*, s1; 3psen*, t1), however due to the short lifetime of the excited singlet state, the photosensitiser can only react if it is intimately associated with ...
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cfe41822c59c8c77d3458b58566576711319540a
tetrapyrrolic photosensitisers in the excited singlet state (1psen*,
tetrapyrrolic photosensitisers in the excited singlet state (1psen*, s>0) are relatively efficient at intersystem crossing and can consequently have a high triplet-state quantum yield. the longer lifetime of this species is sufficient to allow the excited triplet state photosensitiser to interact with surrounding bio-m...
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the decay from the excited singlet state (s1)
the decay from the excited singlet state (s1) to the ground state (s0) is via fluorescence (s1 → s0). singlet state lifetimes of excited fluorophores are very short (τ fl. = 10 –10 seconds) since transitions between the same spin states (s → s or t → t) conserve the spin multiplicity of the electron and, according to t...
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90a5215cdfe18f19f4a0b832cbae21c054181e45
when a chromophore molecule, such as a cyclic
when a chromophore molecule, such as a cyclic tetrapyrrolic molecule, absorbs a photon, one of its electrons is promoted into a higher-energy orbital, elevating the chromophore from the ground state (s0) into a short-lived, electronically excited state (s n) composed of vibrational sub-levels (s n ′). the excited chrom...
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when a photosensitiser is in its excited state
when a photosensitiser is in its excited state (3psen*) it can interact with molecular triplet oxygen (o) and produce radicals and reactive oxygen species (ros), crucial to the type ii mechanism. these species include singlet oxygen (o), hydroxyl radicals (oh) and superoxide (o) ions. they can interact with cellular co...
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in air and tissue, molecular oxygen (o) occurs
in air and tissue, molecular oxygen (o) occurs in a triplet state, whereas almost all other molecules are in a singlet state. reactions between triplet and singlet molecules are forbidden by quantum mechanics, making oxygen relatively non-reactive at physiological conditions. a photosensitizer is a chemical compound th...
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c3f03a5f2e557407e815d7863b8ab28bb32908ea
pdt is a multi-stage process. first a photosensitiser,
pdt is a multi-stage process. first a photosensitiser, ideally with negligible toxicity other than its phototoxicity, is administered in the absence of light, either systemically or topically. when a sufficient amount of photosensitiser appears in diseased tissue, the photosensitiser is activated by exposure to light f...
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d522bc02293c8ff12ac778ace489034a59f020c4
pdt applications involve three components: a photosensitizer, a
pdt applications involve three components: a photosensitizer, a light source and tissue oxygen. the wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce radicals and/or reactive oxygen species. these are free radicals (type i) generated through electron abstraction or trans...
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ea58eb60f8b968a12ceadd5bfffa8a351927d5cf
in the early 1950s, kubo transformed research into
in the early 1950s, kubo transformed research into the linear response properties of near-equilibrium condensed-matter systems, in particular the understanding of electron transport and conductivity, through the kubo formalism, a green's function approach to linear response theory for quantum systems. in 1977 ryogo kub...
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ryogo kubo (久保 亮五, kubo ryōgo, february 15,
ryogo kubo (久保 亮五, kubo ryōgo, february 15, 1920 – march 31, 1995) was a japanese mathematical physicist, best known for his works in statistical physics and non-equilibrium statistical mechanics.
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taryck jordan tahid is a canadian professional soccer
taryck jordan tahid is a canadian professional soccer player who plays as a midfielder for vancouver fc in the canadian premier league. he is the youngest player to ever play in a canadian premier league match, as also the youngest goalscorer in league history.
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tahid is eligible to represent canada and ghana
tahid is eligible to represent canada and ghana at international level. in september 2023, he was called up to the canada u17 team for the first time, ahead of a pair of friendlies against brazil. he made his debut for the program on september 29, as a starter in the first friendly. in november 2023, tahid was named to...
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9b02ba7036a47340114ceaa0cae38aa639996f3f
after trialing with the club during pre-season, on
after trialing with the club during pre-season, on may 6, 2023, tahid signed a full professional contract with vancouver fc of the canadian premier league, becoming (at the time) the youngest player to ever sign a canadian premier league standard contract at the age of 16 years and 16 days. he made his professional deb...
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c952d65ddca0fb934aef6d1e237487d0b860b596
in his youth, he also ran track and
in his youth, he also ran track and field, setting the 100m and 200m records for grade 5 boys at the maple ridge-pitt meadows school district elementary track and field championships in 2018. he currently attends maple ridge secondary school.
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tahid was born in maple ridge, british columbia
tahid was born in maple ridge, british columbia and was raised in a ghanaian-canadian family. he began playing youth soccer at age three with new westminster africa united fc, later joining albion fc, in his hometown of maple ridge, british columbia. in 2018, he joined the vancity pro football academy, which was founde...
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527186f80b3fe1b71403fca0a7d9fc0592db3bcf
taryck jordan tahid (born april 21, 2007) is
taryck jordan tahid (born april 21, 2007) is a canadian professional soccer player who plays as a midfielder for vancouver fc in the canadian premier league. he is the youngest player to ever play in a canadian premier league match, as also the youngest goalscorer in league history.
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db304ba5407005a215293cf330ab4a0d4fe35f0d
henry george ferguson was a british mechanic and
henry george ferguson was a british mechanic and inventor who is noted for his role in the development of the modern agricultural tractor and its three point linkage system, for being the first person in ireland to build and fly his own aeroplane, and for developing the first four-wheel drive formula one car, the fergu...
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