14 research outputs found
Minimal Self-Immolative Probe for Multimodal Fluoride Detection
Two single-molecule,
self-immolative fluoride probes, namely <i>tert</i>-butyldimethylsilyl-protected
2- and 4-difluoromethylphenol,
are described. Compared to similar systems previously described, the
probes are characterized by a simpler structure and straightforward,
two-step preparation. Nevertheless, they allow the detection of fluoride
ions at micromolar concentration by the naked eye, UV–vis absorption,
and fluorescence. A detailed investigation of the self-immolative
reaction reveals that the rate-limiting step is the release of the
first fluoride ion from the difluoromethylphenolate intermediate.
Moreover, the mutual position of the difluoromethyl- and <i>tert</i>-butyldimethylsilyl-protected residues has a relevant effect on the
reactivity. Likely, a CF<sub>2</sub>H–O hydrogen bond in the
2-isomer increases the reactivity of the silyl ether toward hydrolytic
cleavage but also stabilizes the phenolate intermediate, slowing the
release of fluoride ions
Toward hydrophobic carminic acid derivatives and their inclusion in polyacrylates.
<p>Carminic acid, a natural hydrophilic dye
extensively used in food and cosmetic industries, is converted in hydrophobic
dyes by acetylation or pivaloylation. These derivatives are successfully used
as biocolorants for polyacrylate objects. Spectroscopic properties of the
carminic acid derivatives in DMSO and in polybutylacrylate are studied by means
of Photoluminescence and Time Resolved Photoluminescence decays, revealing an hypsochromic
effect due to presence of bulky substituents as the acetyl or pivaloyl groups.
Molecular Mechanics and Density Functional Theory (DFT) calculations confirm
the disruption of planarity between the sugar ring and the anthraquinoid system
determined by the esterification. </p
Thiol–ene Mediated Neoglycosylation of Collagen Patches: A Preliminary Study
Despite the relevance of carbohydrates
as cues in eliciting specific
biological responses, the covalent surface modification of collagen-based
matrices with small carbohydrate epitopes has been scarcely investigated.
We report thereby the development of an efficient procedure for the
chemoselective neoglycosylation of collagen matrices (patches) via
a thiol–ene approach, between alkene-derived monosaccharides
and the thiol-functionalized material surface. Synchrotron radiation-induced
X-ray photoelectron spectroscopy (SR-XPS), Fourier transform-infrared
(FT-IR), and enzyme-linked lectin assay (ELLA) confirmed the effectiveness
of the collagen neoglycosylation. Preliminary biological evaluation
in osteoarthritic models is reported. The proposed methodology can
be extended to any thiolated surface for the development of smart
biomaterials for innovative approaches in regenerative medicine
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps
C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes
PolyÂ(2-methyl-2-oxazoline) (PMOXA)
is an alternative promising polymer to polyÂ(ethylene glycol) (PEG)
for design and engineering of macrophage-evading nanoparticles (NPs).
Although PMOXA-engineered NPs have shown comparable pharmacokinetics
and <i>in vivo</i> performance to PEGylated stealth NPs
in the murine model, its interaction with elements of the human innate
immune system has not been studied. From a translational angle, we
studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived
organically modified silica NPs (PMOXA-coated NPs) of approximately
100 nm in diameter with human complement system, blood leukocytes,
and macrophages and compared their performance with PEGylated and
uncoated NP counterparts. Through detailed immunological and proteomic
profiling, we show that PMOXA-coated NPs extensively trigger complement
activation in human sera exclusively through the classical pathway.
Complement activation is initiated by the sensing molecule C1q, where
C1q binds with high affinity (<i>K</i><sub>d</sub> = 11
± 1 nM) to NP surfaces independent of immunoglobulin binding.
C1q-mediated complement activation accelerates PMOXA opsonization
with the third complement protein (C3) through the amplification loop
of the alternative pathway. This promoted NP recognition by human
blood leukocytes and monocyte-derived macrophages. The macrophage
capture of PMOXA-coated NPs correlates with sera donor variability
in complement activation and opsonization but not with other major
corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps