Regis Vanderesse - Academia.edu (original) (raw)
Papers by Regis Vanderesse
Cancer nanotechnology, 2017
Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of... more Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of therapeutics. In the field of photodynamic therapy (PDT), this targeting advantage of NPs could help ensure drug delivery at specific sites. Among the commonly reported NPs for PDT applications, NPs from zinc oxide, titanium dioxide, and fullerene are commonly reported. In addition, graphene has also been reported to be used as NPs albeit being relatively new to this field. In this context, the present review is organized by these different NPs and contains numerous research works related to PDT applications. The effectiveness of these NPs for PDT is discussed in detail by collecting all essential information described in the literature. The information thus assembled could be useful in designing new NPs specific for PDT and/or PTT applications in the future.
Photochemistry and photobiology, Jan 2, 2017
We report the design and synthesis of europium-doped gadolinium oxysulfide nanoscintillators Gd2 ... more We report the design and synthesis of europium-doped gadolinium oxysulfide nanoscintillators Gd2 O2 S:Eu(3+) conjugated with two different photosensitizers (PSs): a zinc chlorin (ZnTPC) and a zinc phtalocyanine (ZnPc) by covalent bonding through a layer of N-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA). These conjugates were designed to be activated under X-ray excitation to allow a photodynamic effect, although this desired outcome was not achieved in this study. The monodispersed nanoparticles of ∼70 nm diameter were pegylated to be stabilized in aqueous suspension. It was shown that the PSs conserved their photophysical properties once conjugated to the nanoscintillator and efficient singlet oxygen was obtained upon photo-irradiation. However, no energy transfer was observed from the nanoscintillator to the photosensitizer neither under photo- nor X-ray irradiation. This article is protected by copyright. All rights reserved.
Current Medicinal Chemistry, 2015
International journal of molecular sciences, Jan 12, 2015
Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely ... more Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated alon...
After a brief summary of the nanoparticles developed in the field of photodynamic therapy (PDT), ... more After a brief summary of the nanoparticles developed in the field of photodynamic therapy (PDT), the presentation will focus on the interest of using of multifunctional nanoparticles for the treatment of malignant gliomas. PDT for brain tumors appears to be complementary to conventional treatments. Number studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and MRI contrast agents, have been designed by our group. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This is the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. Another approach will be also discussed: the combination of radiotherapy and PDT for the treatment of malignant cerebral gliomas, employing scintillating nanoparticles. With this novel therapeutic approach limited light penetration problem could be overcome and activation of the photosensitizer within tumors is performed using ionizing radiation.
Photodiagnosis and Photodynamic Therapy, 2011
We have identified a new family of foldamers, of which the backbone is enriched in nitrogen atoms... more We have identified a new family of foldamers, of which the backbone is enriched in nitrogen atoms that are locally structured by short- distance hydrogen bonds. As short- distance intramol. contacts within the cyclic mols. may be kept cyclofoldamers can be designed. We expected that under favorable conditions, these components could give rise to nanotube formation, of chosen pore diam., due to piling up (stacking) of cycles through π- π- stacking type interactions and /or intramol. H- bonding. Studies were already performed in the lab in order to cyclise oligomers from a specific series NHN- R1 (with R1 = H) . However, these have proved to be insol. beyond the linear tetramer.We showed that the oligomer's soly. can be considerably increased by introducing a benzyl group (R1 = Bn) . These compds. can lead to the corresponding cyclo- oligomers which were studied in order to analyze their conformation. X ray anal. allows us to confirm their nanotubular organization.
Letters in Peptide Science, 1997
Using the Bee-strategy, a step-by-step synthesis on the PAM solid support of three aza-, imino~-a... more Using the Bee-strategy, a step-by-step synthesis on the PAM solid support of three aza-, imino~-and reduced aza-peptide homologues is described. From the same hydrazinocarbonyl peptide-PAM precursor, the coupling of either a Bee-amino acid or a Bee-amino aldehyde gives rise to an aza-peptide or an iminoaza-peptide containing the ca-CO-NH-N~-CO-NI-I-C a or Cr c* surrogate of the peptide motif, respectively. In situ reduction of the latter by NaBH3CN leads to a reduced aza-peptide containing the Ca-CH2-NH-Na-CO-NH-C a moiety. The key step synthesis of the hydrazineearbonyl peptide-PAM precursor is c~ out by coupling on the growing peptide chain the N-Boc-azaamino acid chloride obtained by the action of triphosgene on the corresponding N-Boc-hydrazine. These m~fications have been introduced in position 1-2 of the YLGYLEQLLR benzodiazepine-like decapeptide,
Nanomedicine: Nanotechnology, Biology and Medicine, 2015
Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatment... more Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. Number studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms.
Letters in Peptide Science, 1997
The conformation of a benzodiazepine-like decapeptide corresponding to the YLGYLEQLLR fragment of... more The conformation of a benzodiazepine-like decapeptide corresponding to the YLGYLEQLLR fragment of a casein has been examined in a sodium dodecyl sulfate micellar medium using circular dichroism, two-dimensional 1H NMR spectroscopy and restrained molecular dynamics simulation. The decapeptide adopts an amphipathic 3 l0-helicoid structure in which the E 6-R l0 ionic bridge stabilizes the C-terminus.
PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for diffe... more PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for different kinds of cancer. Among various attempts to enhance the therapeutics efficacy of PDT, the specific delivery of the PhotoSensitizer (PS) in the tumor is expected to increase ...
Advances in Cancer Therapy, 2011
Handbook of Photomedicine, 2013
ABSTRACT Book Description: This book gathers current research from across the globe in the study ... more ABSTRACT Book Description: This book gathers current research from across the globe in the study of brain cancer, cervical cancer and tumor targeting. Some topics discussed in this compilation include emerging targets in cancer therapy and novel nanotechnology-based therapeutic strategies that have been changing the paradigm in cancer treatment; laparascopy and robotics in cervical cancer treatment; the history and current status of glioma therapy and glioma gene therapy; congenital tumors of the central nervous system; a review of tumors of the paranasal sinuses and real-time tumor targeting in external beam radiotherapy. (Imprint: Nova Biomedical Press)
Tetrahedron, 2012
ABSTRACT Different α-hydrazinoesters with high optical purity have been obtained in large scale v... more ABSTRACT Different α-hydrazinoesters with high optical purity have been obtained in large scale via an SN2 protocol. A coupling reaction with a natural amino acid leads to the corresponding dimers, which have been oligomerized in order to obtain the 1:1 [α/α-Nα-hydrazino]mer series. Conformational studies show that these mixed oligomers are self-organized in solution via a succession of γ-turn and hydrazinoturn whatever the absolute configuration of the chiral carbons.
Tetrahedron, 2013
Several phthalocyanines with different peripheral substituents were prepared and characterized by... more Several phthalocyanines with different peripheral substituents were prepared and characterized by MALDI-TOF, 1 H NMR, UVevis, fluorescence, and singlet oxygen quantum yields and retention time in HPLC normal phase. Zinc was used as a central metal ion to increase the photodynamic therapy efficiency. Phthalonitrile or 4-nitro phthalonitriles were used as starting materials. The influence of lipophilicity on the photophysical and photochemical properties was evaluated.
PLoS ONE, 2012
Nanoparticles are widely suggested as targeted drug-delivery systems. In photodynamic therapy (PD... more Nanoparticles are widely suggested as targeted drug-delivery systems. In photodynamic therapy (PDT), the use of multifunctional nanoparticles as photoactivatable drug carriers is a promising approach for improving treatment efficiency and selectivity. However, the conventional cytotoxicity assays are not well adapted to characterize nanoparticles cytotoxic effects and to discriminate early and late cell responses. In this work, we evaluated a real-time label-free cell analysis system as a tool to investigate in vitro cyto-and photocyto-toxicity of nanoparticles-based photosensitizers compared with classical metabolic assays. To do so, we introduced a dynamic approach based on real-time cell impedance monitoring and a mathematical model-based analysis to characterize the measured dynamic cell response. Analysis of real-time cell responses requires indeed new modeling approaches able to describe suited use of dynamic models. In a first step, a multivariate analysis of variance associated with a canonical analysis of the obtained normalized cell index (NCI) values allowed us to identify different relevant time periods following nanoparticles exposure. After light irradiation, we evidenced discriminant profiles of cell index (CI) kinetics in a concentration-and light dose-dependent manner. In a second step, we proposed a full factorial design of experiments associated with a mixed effect kinetic model of the CI time responses. The estimated model parameters led to a new characterization of the dynamic cell responses such as the magnitude and the time constant of the transient phase in response to the photo-induced dynamic effects. These parameters allowed us to characterize totally the in vitro photodynamic response according to nanoparticle-grafted photosensitizer concentration and light dose. They also let us estimate the strength of the synergic photodynamic effect. This dynamic approach based on statistical modeling furnishes new insights for in vitro characterization of nanoparticles-mediated effects on cell proliferation with or without light irradiation.
Photodiagnosis and Photodynamic Therapy, 2011
Cancer nanotechnology, 2017
Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of... more Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of therapeutics. In the field of photodynamic therapy (PDT), this targeting advantage of NPs could help ensure drug delivery at specific sites. Among the commonly reported NPs for PDT applications, NPs from zinc oxide, titanium dioxide, and fullerene are commonly reported. In addition, graphene has also been reported to be used as NPs albeit being relatively new to this field. In this context, the present review is organized by these different NPs and contains numerous research works related to PDT applications. The effectiveness of these NPs for PDT is discussed in detail by collecting all essential information described in the literature. The information thus assembled could be useful in designing new NPs specific for PDT and/or PTT applications in the future.
Photochemistry and photobiology, Jan 2, 2017
We report the design and synthesis of europium-doped gadolinium oxysulfide nanoscintillators Gd2 ... more We report the design and synthesis of europium-doped gadolinium oxysulfide nanoscintillators Gd2 O2 S:Eu(3+) conjugated with two different photosensitizers (PSs): a zinc chlorin (ZnTPC) and a zinc phtalocyanine (ZnPc) by covalent bonding through a layer of N-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA). These conjugates were designed to be activated under X-ray excitation to allow a photodynamic effect, although this desired outcome was not achieved in this study. The monodispersed nanoparticles of ∼70 nm diameter were pegylated to be stabilized in aqueous suspension. It was shown that the PSs conserved their photophysical properties once conjugated to the nanoscintillator and efficient singlet oxygen was obtained upon photo-irradiation. However, no energy transfer was observed from the nanoscintillator to the photosensitizer neither under photo- nor X-ray irradiation. This article is protected by copyright. All rights reserved.
Current Medicinal Chemistry, 2015
International journal of molecular sciences, Jan 12, 2015
Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely ... more Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated alon...
After a brief summary of the nanoparticles developed in the field of photodynamic therapy (PDT), ... more After a brief summary of the nanoparticles developed in the field of photodynamic therapy (PDT), the presentation will focus on the interest of using of multifunctional nanoparticles for the treatment of malignant gliomas. PDT for brain tumors appears to be complementary to conventional treatments. Number studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and MRI contrast agents, have been designed by our group. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This is the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms. Another approach will be also discussed: the combination of radiotherapy and PDT for the treatment of malignant cerebral gliomas, employing scintillating nanoparticles. With this novel therapeutic approach limited light penetration problem could be overcome and activation of the photosensitizer within tumors is performed using ionizing radiation.
Photodiagnosis and Photodynamic Therapy, 2011
We have identified a new family of foldamers, of which the backbone is enriched in nitrogen atoms... more We have identified a new family of foldamers, of which the backbone is enriched in nitrogen atoms that are locally structured by short- distance hydrogen bonds. As short- distance intramol. contacts within the cyclic mols. may be kept cyclofoldamers can be designed. We expected that under favorable conditions, these components could give rise to nanotube formation, of chosen pore diam., due to piling up (stacking) of cycles through π- π- stacking type interactions and /or intramol. H- bonding. Studies were already performed in the lab in order to cyclise oligomers from a specific series NHN- R1 (with R1 = H) . However, these have proved to be insol. beyond the linear tetramer.We showed that the oligomer's soly. can be considerably increased by introducing a benzyl group (R1 = Bn) . These compds. can lead to the corresponding cyclo- oligomers which were studied in order to analyze their conformation. X ray anal. allows us to confirm their nanotubular organization.
Letters in Peptide Science, 1997
Using the Bee-strategy, a step-by-step synthesis on the PAM solid support of three aza-, imino~-a... more Using the Bee-strategy, a step-by-step synthesis on the PAM solid support of three aza-, imino~-and reduced aza-peptide homologues is described. From the same hydrazinocarbonyl peptide-PAM precursor, the coupling of either a Bee-amino acid or a Bee-amino aldehyde gives rise to an aza-peptide or an iminoaza-peptide containing the ca-CO-NH-N~-CO-NI-I-C a or Cr c* surrogate of the peptide motif, respectively. In situ reduction of the latter by NaBH3CN leads to a reduced aza-peptide containing the Ca-CH2-NH-Na-CO-NH-C a moiety. The key step synthesis of the hydrazineearbonyl peptide-PAM precursor is c~ out by coupling on the growing peptide chain the N-Boc-azaamino acid chloride obtained by the action of triphosgene on the corresponding N-Boc-hydrazine. These m~fications have been introduced in position 1-2 of the YLGYLEQLLR benzodiazepine-like decapeptide,
Nanomedicine: Nanotechnology, Biology and Medicine, 2015
Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatment... more Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments. Number studies show the major role of the vascular effect in the tumor eradication by PDT. For interstitial PDT (iPDT) of brain tumors guided by real-time imaging, multifunctional nanoparticles consisting of a surface-localized tumor vasculature targeting neuropilin-1 (NRP-1) peptide and encapsulated photosensitizer and magnetic resonance imaging (MRI) contrast agents, have been designed. Nanoplatforms confer photosensitivity to cells and demonstrate a molecular affinity to NRP-1. Intravenous injection into rats bearing intracranial glioma exhibited a dynamic contrast-enhanced MRI for angiogenic endothelial cells lining the neovessels mainly located in the peripheral tumor. By using MRI completed by NRP-1 protein expression of the tumor and brain adjacent to tumor tissues, we checked the selectivity of the nanoparticles. This study represents the first in vivo proof of concept of closed-head iPDT guided by real-time MRI using targeted ultrasmall nanoplatforms.
Letters in Peptide Science, 1997
The conformation of a benzodiazepine-like decapeptide corresponding to the YLGYLEQLLR fragment of... more The conformation of a benzodiazepine-like decapeptide corresponding to the YLGYLEQLLR fragment of a casein has been examined in a sodium dodecyl sulfate micellar medium using circular dichroism, two-dimensional 1H NMR spectroscopy and restrained molecular dynamics simulation. The decapeptide adopts an amphipathic 3 l0-helicoid structure in which the E 6-R l0 ionic bridge stabilizes the C-terminus.
PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for diffe... more PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for different kinds of cancer. Among various attempts to enhance the therapeutics efficacy of PDT, the specific delivery of the PhotoSensitizer (PS) in the tumor is expected to increase ...
Advances in Cancer Therapy, 2011
Handbook of Photomedicine, 2013
ABSTRACT Book Description: This book gathers current research from across the globe in the study ... more ABSTRACT Book Description: This book gathers current research from across the globe in the study of brain cancer, cervical cancer and tumor targeting. Some topics discussed in this compilation include emerging targets in cancer therapy and novel nanotechnology-based therapeutic strategies that have been changing the paradigm in cancer treatment; laparascopy and robotics in cervical cancer treatment; the history and current status of glioma therapy and glioma gene therapy; congenital tumors of the central nervous system; a review of tumors of the paranasal sinuses and real-time tumor targeting in external beam radiotherapy. (Imprint: Nova Biomedical Press)
Tetrahedron, 2012
ABSTRACT Different α-hydrazinoesters with high optical purity have been obtained in large scale v... more ABSTRACT Different α-hydrazinoesters with high optical purity have been obtained in large scale via an SN2 protocol. A coupling reaction with a natural amino acid leads to the corresponding dimers, which have been oligomerized in order to obtain the 1:1 [α/α-Nα-hydrazino]mer series. Conformational studies show that these mixed oligomers are self-organized in solution via a succession of γ-turn and hydrazinoturn whatever the absolute configuration of the chiral carbons.
Tetrahedron, 2013
Several phthalocyanines with different peripheral substituents were prepared and characterized by... more Several phthalocyanines with different peripheral substituents were prepared and characterized by MALDI-TOF, 1 H NMR, UVevis, fluorescence, and singlet oxygen quantum yields and retention time in HPLC normal phase. Zinc was used as a central metal ion to increase the photodynamic therapy efficiency. Phthalonitrile or 4-nitro phthalonitriles were used as starting materials. The influence of lipophilicity on the photophysical and photochemical properties was evaluated.
PLoS ONE, 2012
Nanoparticles are widely suggested as targeted drug-delivery systems. In photodynamic therapy (PD... more Nanoparticles are widely suggested as targeted drug-delivery systems. In photodynamic therapy (PDT), the use of multifunctional nanoparticles as photoactivatable drug carriers is a promising approach for improving treatment efficiency and selectivity. However, the conventional cytotoxicity assays are not well adapted to characterize nanoparticles cytotoxic effects and to discriminate early and late cell responses. In this work, we evaluated a real-time label-free cell analysis system as a tool to investigate in vitro cyto-and photocyto-toxicity of nanoparticles-based photosensitizers compared with classical metabolic assays. To do so, we introduced a dynamic approach based on real-time cell impedance monitoring and a mathematical model-based analysis to characterize the measured dynamic cell response. Analysis of real-time cell responses requires indeed new modeling approaches able to describe suited use of dynamic models. In a first step, a multivariate analysis of variance associated with a canonical analysis of the obtained normalized cell index (NCI) values allowed us to identify different relevant time periods following nanoparticles exposure. After light irradiation, we evidenced discriminant profiles of cell index (CI) kinetics in a concentration-and light dose-dependent manner. In a second step, we proposed a full factorial design of experiments associated with a mixed effect kinetic model of the CI time responses. The estimated model parameters led to a new characterization of the dynamic cell responses such as the magnitude and the time constant of the transient phase in response to the photo-induced dynamic effects. These parameters allowed us to characterize totally the in vitro photodynamic response according to nanoparticle-grafted photosensitizer concentration and light dose. They also let us estimate the strength of the synergic photodynamic effect. This dynamic approach based on statistical modeling furnishes new insights for in vitro characterization of nanoparticles-mediated effects on cell proliferation with or without light irradiation.
Photodiagnosis and Photodynamic Therapy, 2011