UVA光照射内源性光敏剂（维生素B2)产生单线态氧和光动力疗法
2018-11-18 22:00阅读：
Singlet Oxygen Generation by UVA Light
Exposure of Endogenous Photosensitizers
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摘要
已经显示
UVA光（
320-400nm）由于由诸如黄素或
尿刊酸的物质产生单线态氧而在组织中产生有害的生物效应。核黄素（维生素B2)，黄素单核苷酸（
FMN），黄素腺嘌呤二核苷酸（
FAD），
β-烟酰胺腺嘌呤二核苷酸（
NAD）和溶液中的
β-烟酰胺腺嘌呤二核苷酸磷酸（
NADP），尿酸或胆固醇在
355nm激发。
通过在
1270nm处发光的时间分辨测量直接检测单线态氧。
NAD，
NADP和胆固醇显示没有发光信号可能是由于在
355nm处的非常低的吸收系数。
.png "UVA光照射内源性光敏剂（维生素B2)产生单线态氧和光动力疗法")
可以清楚地检测到
尿刊酸的单线态氧发光，但信号太弱而无法量化量子产率。核黄素（ΦΔ
=
0.54±0.07），
FMN（
ΦΔ=
0.51±0.07）和
FAD（
ΦΔ=
0.07±0.02）精确测定单线态氧的量子产率。
在充气溶液中，核黄素和FMN比外源光敏剂如Photofrin产生更多的单线态氧，后者用于光动力疗法以杀死癌细胞。
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随着氧浓度的降低，单线态氧产生的量子产率降低，这在评估单线态氧在低氧浓度（组织内部）中的作用时必须考虑。
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Abstract
UVA light (320–400 nm) has been shown to
produce deleterious biological effects in tissue due to the
generation of singlet oxygen by substances like flavins or urocanic
acid. Riboflavin, flavin mononucleotide (FMN), flavin adenine
dinucleotide (FAD), β-nicotinamide adenine dinucleotide (NAD), and
β-nicotinamide adenine dinucleotide phosphate (NADP), urocanic
acid, or cholesterol in solution were excited at 355
nm.
Singlet oxygen was directly detected by
time-resolved measurement of its luminescence at 1270 nm. NAD,
NADP, and cholesterol showed no luminescence signal possibly due to
the very low absorption coefficient at 355 nm.
Singlet oxygen luminescence of urocanic acid
was clearly detected but the signal was too weak to quantify a
quantum yield. The quantum yield of singlet oxygen was precisely
determined for riboflavin (ΦΔ = 0.54 ± 0.07), FMN (ΦΔ = 0.51 ±
0.07), and FAD (ΦΔ = 0.07 ± 0.02).
In aerated solution, riboflavin and FMN
generate more singlet oxygen than exogenous photosensitizers such
as Photofrin, which are applied in photodynamic therapy to kill
cancer cells.
With decreasing oxygen concentration, the
quantum yield of singlet oxygen generation decreased, which must be
considered when assessing the role of singlet oxygen at low oxygen
concentrations (inside tissue).
SOURCE:
Jürgen Baier,* Tim Maisch,* Max Maier,† Eva Engel,‡ Michael
Landthaler,* and Wolfgang Bäumler*
Department of Dermatology, †Department of Physics, and
‡Department of Organic Chemistry, University of Regensburg,
Regensburg, Germany
Singlet Oxygen Generation by UVA Light
Exposure of Endogenous Photosensitizers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518628/
Photodynamic
therapy
From Wikipedia, the free encyclopedia
Synonyms
photochemotherapy
Photodynamic therapy (PDT), is a form of phototherapy
involving light and a photosensitizing chemical substance, used in
conjunction with molecular oxygen to elicit cell death
(phototoxicity). PDT has proven ability to kill microbial cells,
including bacteria, fungi and viruses.[1] PDT is popularly used in
treating acne. It is used clinically to treat a wide range of
medical conditions, including wet age-related macular degeneration,
psoriasis, atherosclerosis and has shown some efficacy in
anti-viral treatments, including herpes. It also treats malignant
cancers[2] including head and neck, lung, bladder and particular
skin. The technology has also been tested for treatment of prostate
cancer, both in a dog model[3] and in human prostate cancer
patients.[4]
It is recognised as a treatment strategy that is both
minimally invasive and minimally toxic. Other light-based and laser
therapies such as laser wound healing and rejuvenation, or intense
pulsed light hair removal do not require a photosensitizer.[5]
Photosensitisers have been employed to sterilise blood plasma and
water in order to remove blood-borne viruses and microbes and have
been considered for agricultural uses, including herbicides and
insecticides.
Photodynamic therapy's advantages lessen the need for
delicate surgery and lengthy recuperation and minimal formation of
scar tissue and disfigurement. A side effect is the associated
photosensitisation of skin tissue.[5]
Basics
PDT applications involve three components:[2] 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 transfer from a substrate molecule and highly
reactive state of oxygen known as singlet oxygen (Type
II).
PDT is a multi-stage process. First a photosensitiser with
negligible dark toxicity is administered, either systemically or
topically, in the absence of light. When a sufficient amount of
photosensitiser appears in diseased tissue, the photosensitiser is
activated by exposure to light for a specified period. The light
dose supplies sufficient energy to stimulate the photosensitiser,
but not enough to damage neighbouring healthy tissue. The reactive
oxygen kills the target cells.[5]
Reactive oxygen species
In air and tissue, molecular oxygen (O2) 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
that can be promoted to an excited state upon absorption of light
and undergo intersystem crossing (ISC) with oxygen to produce
singlet oxygen. This species is highly cytotoxic, rapidly attacking
any organic compounds it encounters. It is rapidly eliminated from
cells, in an average of 3 µs.[6]
Photochemical processes
When a photosensitiser is in its excited state (3Psen*) it
can interact with molecular triplet oxygen (3O2) and produce
radicals and reactive oxygen species (ROS), crucial to the Type II
mechanism. These species include singlet oxygen (1O2), hydroxyl
radicals (•OH) and superoxide (O2−) ions.
They can interact with cellular components including unsaturated
lipids, amino acid residues and nucleic acids. If sufficient
oxidative damage ensues, this will result in target-cell death
(only within the illuminated area).[5]
Photosensitisers
----Some photosensitizers；riboflavin,rose bengal,
methylene, chorophyll
Many photosensitizers for PDT exist. They divide into
porphyrins, chlorins and dyes.[7] Examples include aminolevulinic
acid (ALA), Silicon Phthalocyanine Pc 4,
m-tetrahydroxyphenylchlorin (mTHPC) and mono-L-aspartyl
chlorin e6 (NPe6).
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,[7][8] Amphinex[9] and Azadipyrromethenes.
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.[10] In contrast, ALA localizes in the mitochondria[11]
and methylene blue in the lysosomes.[12]
Cyclic tetrapyrrolic chromophores
Cyclic tetrapyrrolic molecules are fluorophores and
photosensitisers. Cyclic tetrapyrrolic derivatives have an inherent
similarity to the naturally occurring porphyrins present in living
matter.
Porphyrins
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. Porphyrins are tetrapyrrolic molecules, with the heart of
the skeleton a heterocyclic macrocycle, known as a porphine. The
fundamental porphine frame consists of four pyrrolic sub-units
linked on opposing sides (α-positions, numbered 1, 4, 6, 9, 11, 14,
16 and 19) through four methine (CH) bridges (5, 10, 15 and 20),
known as the meso-carbon atoms/positions. The resulting conjugated
planar macrocycle may be substituted at the meso- and/or
β-positions (2, 3, 7, 8, 12, 13, 17 and 18): if the meso- and
β-hydrogens are substituted with non-hydrogen atoms or groups, the
resulting compounds are known as porphyrins.[5]
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
complexes with most metals.[5]
Absorption spectroscopy
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
