Author
Lina Bezdetnaya
Other affiliations: Centre national de la recherche scientifique, Nancy-Université
Bio: Lina Bezdetnaya is an academic researcher from University of Lorraine. The author has contributed to research in topics: Temoporfin & Photodynamic therapy. The author has an hindex of 33, co-authored 119 publications receiving 3682 citations. Previous affiliations of Lina Bezdetnaya include Centre national de la recherche scientifique & Nancy-Université.
Papers published on a yearly basis
Papers
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TL;DR: The synthesis of CuInS(2)/ZnS core/shell QDs emitting in the NIR with good quantum yield and stability even after transfer into water is presented and compared to their Cd-containing counterparts to show a clear difference in acute local toxicity.
Abstract: Semiconductor quantum dots (QDs) could significantly impact the performance of biomedical near-infrared (NIR) imaging by providing fluorescent probes that are brighter and more photostable than conventional organic dyes. However, the toxicity of the components of NIR emitting II−VI and IV−VI QDs that have been made so far (Cd, Hg, Te, Pb, etc.) has remained a major obstacle to the clinical use of QDs. Here, we present the synthesis of CuInS2/ZnS core/shell QDs emitting in the NIR (∼800 nm) with good quantum yield and stability even after transfer into water. We demonstrate the potential of these QDs by imaging two regional lymph nodes (LNs) in vivo in mice. We then compare the inflammatory response of the axillary LN induced by different doses of CuInS2/ZnS and CdTeSe/CdZnS QDs and show a clear difference in acute local toxicity, the onset of inflammation only occurring at a 10 times more concentrated dose for CuInS2/ZnS QDs than for their Cd-containing counterparts.
502 citations
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TL;DR: Results support the assumption that c-PARP expression was dependent on treatment-induced apoptosis and shows the relevance of using antibodies that can discriminate caspase-dependent apoptotic pathways.
Abstract: Immunohistochemistry to active caspase-3, recently recommended for apoptosis detection, is inappropriate to detect apoptosis involving caspase-7. Cleavage of poly-ADP-ribose polymerase 1 (PARP-1), a major substrate of both caspases, is a valuable marker of apoptosis. Apoptosis evaluation induced in vitro either by paclitaxel or by photodynamic treatment (PDT) with Foscan in HT29 or KB monolayer cells and HT29 spheroids yielded a close percentage of labeled cells whatever the antibody used, whereas in control specimens, cleaved PARP (c-PARP) immunostaining failed to detect apoptosis as efficiently as active caspase-3 or -7 immunostaining. Studies in MDA-MB231 monolayer cells and HT29 xenografts either subjected or not subjected to Foscan-PDT resulted in a significant higher number of active caspase-3-labeled cells, although immunofluorescence analysis showed c-PARP and active caspase-3 perfectly colocalized in tumors. A restricted expression of c-PARP was obvious in the greater part of caspase-3 expressing cells from control tumor, whereas photosensitized tumors showed a higher number of cells expressing large fluorescent spots from both active caspase-3 and c-PARP. These results support the assumption that c-PARP expression was dependent on treatment-induced apoptosis. The absence of caspase-7 activation in some caspase-3-expressing cells undergoing Foscan-PDT shows the relevance of using antibodies that can discriminate caspase-dependent apoptotic pathways.
213 citations
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TL;DR: In this paper, a simple one-pot synthetic route without injection was presented to make fluorescent sphalerite Cu−In−Se core and ZnS core/shell QDs, which can be tuned from ∼700 nm to ∼1 μm depending on the QD size.
Abstract: Near-infrared (NIR) semiconductor quantum dots (QDs) represent promising fluorescent probes for biological and biomedical imaging. CuInSe2 is a good candidate for these applications due to its bandgap in the near-infrared and the reduced toxicity of its components compared to other NIR QD materials (CdTe, CdHgTe, PbS, etc.). Here we present a simple one-pot synthetic route without injection to make fluorescent sphalerite Cu−In−Se core and Cu−In−Se/ZnS core/shell QDs. We show that the photoluminescence (PL) of the resulting core QDs can be tuned from ∼700 nm to ∼1 μm depending on the QD size (from ∼2 to ∼5 nm in diameter). The optical and structural properties of these QDs are consistent with charge recombination via donor−acceptor levels instead of direct excitonic recombination. Finally, we show that the growth of a ZnS shell around these QDs increases their PL quantum yield substantially (up to 40−50% at 800 nm) and allows preservation of their PL properties after solubilization into water and in vivo, ...
178 citations
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TL;DR: A promising class of near infrared emitting probes based on semiconductor quantum dots (QDs), which have the potential to considerably improve in vivo fluorescence imaging thanks to their high brightness and stability, are reviewed.
153 citations
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TL;DR: This is the first study to demonstrate unambiguously that the endoplasmic reticulum and Golgi apparatus are preferential sites of Foscan® accumulation in the MCF-7 cell line.
Abstract: Intracellular photosensitiser localisation significantly influences the mechanism of response to photodynamic therapy (PDT), since the primary sites of damage are closely related to the specific sensitiser distribution Foscan subcellular localisation in the MCF-7 human adenocarcinoma cell line has been studied by means of confocal microscopy and microspectrofluorometry The fluorescence topographic profiles recorded after cells costained with Foscan and organelle-specific fluorescent probes revealed that Foscan presents low localisation in lysosomes and a weak accumulation in mitochondria Alternatively, the Foscan fluorescence topographic profile turned out to colocalise perfectly with that obtained for the endoplasmic reticulum (ER) and the Golgi apparatus The patterns of fluorescence derived from confocal microscopy studies were consistent with predominant localisation of Foscan in these organelles Furthermore, evaluation of enzymatic activity of selected organelles immediately after laser light irradiation (650 nm) indicated the Golgi apparatus and ER as the primary damaged sites resulting from Foscan-mediated PDT in the MCF-7 cell line To our knowledge, this is the first study to demonstrate unambiguously that the ER and the Golgi apparatus are preferential sites of Foscan accumulation
144 citations
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TL;DR: The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.
Abstract: The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.
4,270 citations
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Katholieke Universiteit Leuven1, Oslo University Hospital2, University of Pennsylvania3, University of Rochester4, Medical College of Wisconsin5, Roswell Park Cancer Institute6, Harvard University7, Massachusetts Institute of Technology8, Wayne State University9, University of British Columbia10, University of Oslo11, Medical University of Warsaw12, University of Liège13, University of Toronto14, Polish Academy of Sciences15
TL;DR: The photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells as discussed by the authors, which can prolong survival in patients with inoperable cancers and significantly improve quality of life.
Abstract: Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281. V C
3,770 citations
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TL;DR: This paper presents a meta-modelling study of the response of the immune system to chemotherapy and its applications in the context of central nervous system disorders.
Abstract: Sasidharan Swarnalatha Lucky,†,§ Khee Chee Soo,‡ and Yong Zhang*,†,§,∥ †NUS Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore, Singapore, Singapore 117456 ‡Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore 169610 Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore 117576 College of Chemistry and Life Sciences, Zhejiang Normal University, Zhejiang, P. R. China 321004
2,194 citations
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TL;DR: Photodynamic therapy uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system.
Abstract: Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.
2,150 citations
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TL;DR: This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications.
Abstract: Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.
1,891 citations