خدمة تلخيص النصوص العربية أونلاين،قم بتلخيص نصوصك بضغطة واحدة من خلال هذه الخدمة
INTRODUCTION
Porphyrins and their general derivatives (porphyrinoids) are
pyrrole containing macrocycles with elaborate pi-conjugation
pathways that result in vibrant colors observable by the naked
eye.The
scheme also shows some subsequent biomedical and light?harvesting applications that can be achieved.Type II reactions
function by conversion of the ground-state triplet oxygen
(
3
O2) to its reactive singlet state (1
O2). The other photosensitizer-based therapeutic modalities are
newer technologies but are also promising. For example, the
purpose of PACT is to treat infections with the ability to also
overcome multidrug resistance. In terms of photosensitizers being investigated for these
biomedical applications, porphyrinoids have been used the
most owing to their unique properties. These include their
ability to efficiently absorb visible red light (high extinction
coefficients), their long T1 state lifetimes (providing time to
form ROS species and in particular generation of 1
O2 with
high yield), facile synthetic functionalization, structural
diversity, and minimal dark toxicity (Kou et al., 2017; Lin
et al., 2020).In addition to classical photophysical
and photochemical research (such as electron transfer, solar cells,
and artificial light-harvesting) (Hsiao et al., 1996; Aratani et al.,
2009; Beletskaya et al., 2009; Tanaka and Osuka, 2015; Zhang and
Ying, 2015), researchers have focused on promising biomedical
applications where porphyrins serve as photosensitizers
(O'Connor et al., 2009) in e.g., photodynamic therapy (PDT),
photodynamic antimicrobial chemotherapy (PACT) (Liu et al.,
2012; Dosselli et al., 2013; Pereira et al., 2014; Meng et al., 2015;
Yuan et al., 2017), photothermal therapy (PTT) (Zou et al., 2017),
and as chromophores for biological imaging (Sibrian-Vazquez
et al., 2005; Giuntini et al., 2011; Dondi et al., 2016).Further, porphyrin-biomacromolecule conjugation, in tandem
with synthetic manipulation of the porphyrin peripheral
substituents and metalation state, can result in modulation of
key porphyrin features needed for biomedical applications (e.g.,
multiple absorption bands, emission near the far-red region of the
visible electromagnetic spectrum, good photostability, and low
dark toxicity).These
biomolecules are highly complex and contain multiple reactive
functional groups and thus the methods used to selectively attach
porphyrins to targeted sites on these biomacromolecules are also
instructive for the general tethering of functional entities onto
such biomolecules.In many of the photosensitizer-based biomedical
applications, the typically hydrophobic porphyrinoids need to be
1) solubilized in water, 2) inhibited from aggregation, and 3) also
are required to localize selectively in target cells and tissue
(Hamblin and Mroz, 2008).In addition to utilizing naturally occurring
reactive groups (e.g., amines and thiols), this manuscript will also
discuss key bioorthogonal reactions that can be employed to
facilitate porphyrin-biomacromolecule conjugation (Table 1).More than mere aesthetics, biology
harnesses the unique photophysical and chemical properties of
porphyrinoids to drive immensely important processes including
photosynthesis, blood oxygenation, and substrate oxidation.On the other hand, PTT
facilitates tumor cell death by a thermal ablation mechanism,
where the photosensitizer (i.e., photothermal agent) is designed to
produce heat energy upon light irradiation (instead of
fluorescence emission and production of singlet oxygen
species).The bioorthogonal reactions are judiciously designed, with
customized reactive partners, to be highly selective and do not
readily react with other biological/chemical entities present in
living cells/systems under physiological conditions (ambient
temperature and pressure, neutral pH, and aqueous media).This review will focus on the novel methods developed and key
applications that are uncovered by covalently linking
porphyrinoids to three main classes of biomacromolecules:
oligonucleotides (ONs), peptides and antibodies. Further, bioorthogonal reactions, in general, should meet the
criteria of kinetic-, thermodynamic-, and metabolic-stability,
without generating materials toxic to living systems (Lang and
Chin, 2014; Devaraj, 2018).Scheme 1 illustrates some common
functionalities (naturally present or synthetically modified) in
porphyrinoids as well as ONs and peptides that have been utilized
to generate porphyrin-biomacromolecule conjugates. From the abovementioned therapeutic modalities, PDT has
been the most investigated and is used in the clinic to treat various
cancers (including tumors of the esophagus, skin, head, neck,
bladder, and lung).This modality follows the same
principle of PDT in terms of production of ROS that are lethal to
microbial pathogens (Meng et al., 2015).Importantly, these photothermal agents can also have
applications as contrast agents for photoacoustic imaging (which
has deeper penetration in biological tissues) (Zou et al., 2017).Indeed, the green colors in plants are due to the absorption
capacity of the porphyrinoid cholorophyll A and its degradation,
in the Fall, leads to other chromophores becoming more visible as
orange and brown hues.Subsequent irradiation of low-energy,
tissue penetrating, light of appropriate wavelength (typically red
light) leads to the activation of the photosensitizer from its
ground state (S0) to the first excited singlet state (S1).Type I reactions involve hydrogen or electron
transfer between the T1 photosensitizer and biomolecules
creating reactive radicals and other ROS.In
these processes, the pophyrinoid cores interact with and are
properly sequestered by, protein macromolecules that tune the
activity of the macrocycles.In this
method, a photosensitizer first localizes in specific tumor tissue
after intravenous injection.Population of the T1 state can lead to two different
pathways of creating reactive oxygen species (ROS) necessary to
initiate cell death.The S1
state can release its energy by various pathways including
emission of light as fluorescence or radiation-less transition.For PDT applications, an intersystem crossing takes place,
transferring energy from the S1 state to the longer lived triplet
state (T1).Singlet oxygen leads to
tissue destruction and apoptosis (O'Connor et al., 2009).The following
sections will expound on these conjugation chemistries and
applications.Non-covalent interactions of
porphyrinoids with biomacromolecules is also an area of
active research.The judicious conjugation of
porphyrins to biomacromolecules can address these issues.Also, it should be noted that the focus herein will
be on covalent tethering.For example, porphyrinoids binding to
peptides and proteins have beThe reason for the adoption of PDT in the
clinic is because it is generally safe and has few side effects.
INTRODUCTION
Porphyrins and their general derivatives (porphyrinoids) are
pyrrole containing macrocycles with elaborate pi-conjugation
pathways that result in vibrant colors observable by the naked
eye. Indeed, the green colors in plants are due to the absorption
capacity of the porphyrinoid cholorophyll A and its degradation,
in the Fall, leads to other chromophores becoming more visible as
orange and brown hues. More than mere aesthetics, biology
harnesses the unique photophysical and chemical properties of
porphyrinoids to drive immensely important processes including
photosynthesis, blood oxygenation, and substrate oxidation. In
these processes, the pophyrinoid cores interact with and are
properly sequestered by, protein macromolecules that tune the
activity of the macrocycles. In addition to classical photophysical
and photochemical research (such as electron transfer, solar cells,
and artificial light-harvesting) (Hsiao et al., 1996; Aratani et al.,
2009; Beletskaya et al., 2009; Tanaka and Osuka, 2015; Zhang and
Ying, 2015), researchers have focused on promising biomedical
applications where porphyrins serve as photosensitizers
(O’Connor et al., 2009) in e.g., photodynamic therapy (PDT),
photodynamic antimicrobial chemotherapy (PACT) (Liu et al.,
2012; Dosselli et al., 2013; Pereira et al., 2014; Meng et al., 2015;
Yuan et al., 2017), photothermal therapy (PTT) (Zou et al., 2017),
and as chromophores for biological imaging (Sibrian-Vazquez
et al., 2005; Giuntini et al., 2011; Dondi et al., 2016).
From the abovementioned therapeutic modalities, PDT has
been the most investigated and is used in the clinic to treat various
cancers (including tumors of the esophagus, skin, head, neck,
bladder, and lung). The reason for the adoption of PDT in the
clinic is because it is generally safe and has few side effects. In this
method, a photosensitizer first localizes in specific tumor tissue
after intravenous injection. Subsequent irradiation of low-energy,
tissue penetrating, light of appropriate wavelength (typically red
light) leads to the activation of the photosensitizer from its
ground state (S0) to the first excited singlet state (S1). The S1
state can release its energy by various pathways including
emission of light as fluorescence or radiation-less transition.
For PDT applications, an intersystem crossing takes place,
transferring energy from the S1 state to the longer lived triplet
state (T1). Population of the T1 state can lead to two different
pathways of creating reactive oxygen species (ROS) necessary to
initiate cell death. Type I reactions involve hydrogen or electron
transfer between the T1 photosensitizer and biomolecules
creating reactive radicals and other ROS. Type II reactions
function by conversion of the ground-state triplet oxygen
(
3
O2) to its reactive singlet state (1
O2). Singlet oxygen leads to
tissue destruction and apoptosis (O’Connor et al., 2009).
The other photosensitizer-based therapeutic modalities are
newer technologies but are also promising. For example, the
purpose of PACT is to treat infections with the ability to also
overcome multidrug resistance. This modality follows the same
principle of PDT in terms of production of ROS that are lethal to
microbial pathogens (Meng et al., 2015). On the other hand, PTT
facilitates tumor cell death by a thermal ablation mechanism,
where the photosensitizer (i.e., photothermal agent) is designed to
produce heat energy upon light irradiation (instead of
fluorescence emission and production of singlet oxygen
species). Importantly, these photothermal agents can also have
applications as contrast agents for photoacoustic imaging (which
has deeper penetration in biological tissues) (Zou et al., 2017).
In terms of photosensitizers being investigated for these
biomedical applications, porphyrinoids have been used the
most owing to their unique properties. These include their
ability to efficiently absorb visible red light (high extinction
coefficients), their long T1 state lifetimes (providing time to
form ROS species and in particular generation of 1
O2 with
high yield), facile synthetic functionalization, structural
diversity, and minimal dark toxicity (Kou et al., 2017; Lin
et al., 2020). In many of the photosensitizer-based biomedical
applications, the typically hydrophobic porphyrinoids need to be
تلخيص النصوص العربية والإنجليزية اليا باستخدام الخوارزميات الإحصائية وترتيب وأهمية الجمل في النص
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