@article{lecuyer_fate_2022,
title = {Fate and biological impact of persistent luminescence nanoparticles after injection in mice: a one-year follow-up},
author = {Thomas L\'{e}cuyer and Johanne Seguin and Alice Balfourier and Marine Delagrange and Pierre Burckel and Ren\'{e} Lai-Kuen and Virginie Mignon and Bertrand Ducos and Michael Tharaud and Bruno Saubam\'{e}a and Daniel Scherman and Nathalie Mignet and Florence Gazeau and Cyrille Richard},
doi = {10.1039/D2NR03546D},
issn = {2040-3364, 2040-3372},
year = {2022},
date = {2022-01-01},
urldate = {2022-10-17},
journal = {Nanoscale},
pages = {10.1039.D2NR03546D},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{balfourier_importance_2022,
title = {Importance of Metal Biotransformation in Cell Response to Metallic Nanoparticles: A Transcriptomic Meta-analysis Study},
author = {Alice Balfourier and Anne-Pia Marty and Florence Gazeau},
doi = {10.1021/acsnanoscienceau.2c00035},
issn = {2694-2496, 2694-2496},
year = {2022},
date = {2022-01-01},
urldate = {2023-01-06},
journal = {ACS Nanoscience Au},
pages = {acsnanoscienceau.2c00035},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{balfourier2022multiscale,
title = {Multiscale Multimodal Investigation of the Intratissural Biodistribution of Iron Nanotherapeutics with Single Cell Resolution Reveals Co-Localization with Endogenous Iron in Splenic Macrophages},
author = {Alice Balfourier and Elena Tsolaki and Laura Heeb and Fabian HL Starsich and Daniel Klose and Andreas Boss and Anurag Gupta and Alexander Gogos and Inge K Herrmann},
doi = {10.1002/smtd.202201061},
year = {2022},
date = {2022-01-01},
journal = {Small Methods},
pages = {2201061},
publisher = {Wiley Online Library},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{boss_assessment_nodate,
title = {Assessment of iron nanoparticle distribution in mouse models using ultrashort-echo-time MRI},
author = {Andreas Boss and Laura Heeb and Divya Vats and Fabian H L Starsich and Alice Balfourier and Inge K Herrmann and Anurag Gupta},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/nbm.4690},
doi = {10.1002/nbm.4690},
issn = {1099-1492},
year = {2022},
date = {2022-01-01},
urldate = {2022-04-21},
journal = {NMR in Biomedicine},
pages = {e4690},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{mulens-arias_tumor-selective_2021,
title = {Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil\textendashGold Nanoparticle Complexes},
author = {Vladimir Mulens-Arias and Alba Nicol\'{a}s-Boluda and Amandine Pinto and Alice Balfourier and Florent Carn and Amanda K A Silva and Marc Pocard and Florence Gazeau},
url = {https://pubs.acs.org/doi/10.1021/acsnano.0c10276},
doi = {10.1021/acsnano.0c10276},
issn = {1936-0851, 1936-086X},
year = {2021},
date = {2021-02-01},
urldate = {2022-04-29},
journal = {ACS Nano},
volume = {15},
number = {2},
pages = {3330--3348},
abstract = {Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP−5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP−5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP−drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{balfourier_unexpected_2020,
title = {Unexpected intracellular biodegradation and recrystallization of gold nanoparticles},
author = {Alice Balfourier and Nathalie Luciani and Guillaume Wang and Gerald Lelong and Ovidiu Ersen and Abdelali Khelfa and Damien Alloyeau and Florence Gazeau and Florent Carn},
url = {https://pnas.org/doi/full/10.1073/pnas.1911734116},
doi = {10.1073/pnas.1911734116},
issn = {0027-8424, 1091-6490},
year = {2020},
date = {2020-01-01},
urldate = {2022-03-30},
journal = {Proceedings of the National Academy of Sciences},
volume = {117},
number = {1},
pages = {103--113},
abstract = {Significance
While gold nanoparticles are at the core of an increasing range of medical applications, their fate in the organism has barely been studied so far. Because of their chemical inertness, common belief is that gold nanoparticles remain endlessly intact in tissues. We show that 4- to 22-nm gold nanoparticles are actually degraded in vitro by cells, with a faster degradation of the smallest size. Transcriptomics studies reveal the active role of cell lysosome into this biodissolution. Furthermore, we point out that the released gold recrystallizes into biopersistent nanostructures. Interestingly, these degradation products are similar to previously observed gold deposits in human tissues after gold salts treatment for rheumatoid arthritis, underlying a common metabolism between gold nanoparticles and ionic gold.
,
Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{balfourier_gold-based_2020,
title = {Gold-based therapy: From past to present},
author = {Alice Balfourier and Jelena Kolosnjaj-Tabi and Nathalie Luciani and Florent Carn and Florence Gazeau},
url = {https://www.pnas.org/doi/abs/10.1073/pnas.2007285117},
doi = {10.1073/pnas.2007285117},
year = {2020},
date = {2020-01-01},
urldate = {2022-03-30},
journal = {Proceedings of the National Academy of Sciences},
volume = {117},
number = {37},
pages = {22639--22648},
note = {Publisher: Proceedings of the National Academy of Sciences},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{balfourier_rational_2020,
title = {Rational Design of Fractal Gold Nanosphere Assemblies with Optimized Photothermal Conversion Using a Quantitative Structure Property Relationship (QSPR) Approach},
author = {Alice Balfourier and Vladimir Mulens-Arias and Florence Gazeau and Florent Carn},
url = {https://pubs.acs.org/doi/10.1021/acs.jpcc.0c00384},
doi = {10.1021/acs.jpcc.0c00384},
issn = {1932-7447, 1932-7455},
year = {2020},
date = {2020-01-01},
urldate = {2022-03-31},
journal = {The Journal of Physical Chemistry C},
volume = {124},
number = {16},
pages = {8938--8948},
abstract = {Assemblies of plasmonic nanoparticles have been proposed for various applications, including photothermal therapy, exploiting surface plasmon coupling phenomena. However, the rational design of fractal nanoparticle assembly remains challenging due to the lack of structural characterizations and modelization of real systems. Here we used the quantitative structure property relationship (QSPR) approach, driven by experimental data and statistical analysis, to establish a relationship between structural descriptors of fractal gold nanoparticle (GNP) aggregates and their light-to-heat conversion. A total of 160 assemblies of various size spherical GNPs with different polyelectrolyte chains were synthesized, which differ in their global charge, size, mass fractal dimension, and plasmonic properties. Fifteen independent descriptors of structure and properties were extracted and further analyzed by QSPR. Principal component analysis and multilinear regression reveal that light-to-heat conversion is mainly governed by the structure of the aggregates and not by the characteristics of the building blocks. This highlights the key role of the fractal dimension of the aggregate and of the ratio of GNP/polyelectrolyte mass to optimize photothermal effects. Rational criteria to optimize light-to-heat conversion within nonideal fractal assemblies of GNP were identified, relaxing on the choice of other parameters, such as GNP or aggregate size, that can be adapted to the desired biomedical applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{mulens-arias_endocytosis-driven_2020,
title = {Endocytosis-driven gold nanoparticle fractal rearrangement in cells and its influence on photothermal conversion},
author = {Vladimir Mulens-Arias and Alice Balfourier and Alba Nicol\'{a}s-Boluda and Florent Carn and Florence Gazeau},
url = {http://xlink.rsc.org/?DOI=D0NR05886F},
doi = {10.1039/D0NR05886F},
issn = {2040-3364, 2040-3372},
year = {2020},
date = {2020-01-01},
urldate = {2022-03-31},
journal = {Nanoscale},
volume = {12},
number = {42},
pages = {21832--21849},
abstract = {Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields.
,

Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields. The precise structure, organization, distribution, and density of gold nanoparticles (AuNPs) confined within intracellular compartments such as lysosomes have not been studied comprehensively, hampering the derivation of predictive models of their therapeutic activity within the cells of interest. By using transmission electron microscopy and small-angle X-ray scattering, we have determined that canonical spherical citrate-coated AuNPs in the 3\textendash30 nm size range form fractal clusters in endolysosomes of macrophages, endothelial cells, and colon cancer cells. Statistical analysis revealed that the cluster size and endolysosome size are correlated but do not depend on the size of AuNPs unless larger preformed aggregates of AuNPs are internalized. Smaller AuNPs are confined in greater numbers in loose aggregates covering a higher fraction of the endolysosomes compared to the largest AuNPs. The fractal dimensions of intracellular clusters increased with the particle size, regardless of the cell type. We thus analyzed how these intracellular structure parameters of AuNPs affect their optical absorption and photothermal properties. We observed that a 2
nd
plasmon resonance band was shifted to the near-infrared region when the nanoparticle size and fractal dimensions of the intracellular cluster increased. This phenomenon of intracellular plasmon coupling is not directly correlated to the size of the intralysosomal cluster or the number of AuNPs per cluster but rather to the compacity of the cluster and the size of the individual AuNPs. The intracellular plasmon-coupling phenomenon translates to an efficient heating efficiency with the excitation of the three cell types at 808 nm, transforming the NIR-transparent canonical AuNPs with sizes below 30 nm into NIR-absorbing clusters in the tumor microenvironment. Harnessing the spontaneous clustering of spherical AuNPs by cells might be a more valuable strategy for theranostic purposes than deploying complex engineering to derive NIR-absorbent nanostructures out of their environment. Our paper sheds light on AuNP intracellular reorganization and proposes a general method to link their intracellular fates to their
in situ
physical properties exploited in medical applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{mulens-arias_polyethyleneimine-assisted_2019,
title = {Polyethyleneimine-assisted one-pot synthesis of quasi-fractal plasmonic gold nanocomposites as a photothermal theranostic agent},
author = {Vladimir Mulens-Arias and Alba Nicol\'{a}s-Boluda and Alexandre Gehanno and Alice Balfourier and Florent Carn and Florence Gazeau},
url = {https://pubs.rsc.org/en/content/articlelanding/2019/nr/c8nr09849b},
doi = {10.1039/C8NR09849B},
issn = {2040-3372},
year = {2019},
date = {2019-01-01},
urldate = {2022-03-30},
journal = {Nanoscale},
volume = {11},
number = {7},
pages = {3344--3359},
abstract = {Gold nanoparticles have been thoroughly used in designing thermal ablative therapies and in photoacoustic imaging in cancer treatment owing to their unique and tunable plasmonic properties. While the plasmonic properties highly depend on the size and structure, controllable aggregation of gold nanoparticles can trigger a plasmonic coupling of adjacent electronic clouds, henceforth leading to an increase of light absorption within the near-infrared (NIR) window. Polymer-engraftment of gold nanoparticles has been investigated to achieve the plasmonic coupling phenomenon, but complex chemical steps are often needed to accomplish a biomedically relevant product. An appealing and controllable manner of achieving polymer-based plasmon coupling is a template-assisted Au+3 reduction that ensures in situ gold reduction and coalescence. Among the polymers exploited as reducing agents are polyethyleneimines (PEI). In this study, we addressed the PEI-assisted synthesis of gold nanoparticles and their further aggregation to obtain fractal NIR-absorbent plasmonic nanoaggregates for photothermal therapy and photoacoustic imaging of colorectal cancer. PEI-assisted Au+3 reduction was followed up by UV-visible light absorption, small-angle X-ray scattering (SAXS), and photo-thermal conversion. The reaction kinetics, stability, and the photothermal plasmonic properties of the as-synthesized nanocomposites tightly depended on the PEI : Au ratio. We defined a PEI-Au ratio range (2.5\textendash5) for the one-pot synthesis of gold nanoparticles that self-arrange into fractal nanoaggregates with demonstrated photo-thermal therapeutic and imaging efficiency both in vitro and in vivo in a colorectal carcinoma (CRC) animal model.},
note = {Publisher: The Royal Society of Chemistry},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{mulens-arias_disturbance_2019,
title = {Disturbance of adhesomes by gold nanoparticles reveals a size- and cell type-bias},
author = {Vladimir Mulens-Arias and Alice Balfourier and Alba Nicol\'{a}s-Boluda and Florent Carn and Florence Gazeau},
url = {http://xlink.rsc.org/?DOI=C8BM01267A},
doi = {10.1039/C8BM01267A},
issn = {2047-4830, 2047-4849},
year = {2019},
date = {2019-01-01},
urldate = {2022-03-31},
journal = {Biomaterials Science},
volume = {7},
number = {1},
pages = {389--408},
abstract = {Gold nanoparticles are known multifunctional theranosis agents. Here, we studied the collective dynamics of adhesive F-actin rich structures upon AuNP treatment.
,

Gold nanoparticles (AuNP) have been thoroughly studied as multifunctional theranosis agents for cell imaging and cancer therapy as well as sensors due to their tunable physical and chemical properties. Although AuNP have proved to be safe in a wide concentration range, yet other important biological effects can arise in the sublethal window of treatment. This is especially pivotal to understand how AuNP can affect cell biology when labeling steps are needed for cell tracking
in vivo
, as nanoparticle loading can affect cell migratory/invasion ability, a function mediated by filamentous actin-rich nanometric structures collectively called adhesomes. It is noteworthy that, although numerous research studies have addressed the cell response to AuNP loading, yet none of them focuses on adhesome dynamics as a target of intracellular pathways affected by AuNP. We intend to study the collective dynamics of adhesive F-actin rich structures upon AuNP treatment as an approach to understand the complex AuNP-triggered modulation of migration/invasion related cellular functions. We demonstrated that citrate-coated spherical AuNP of different sizes (3, 11, 16, 30 and 40 nm) disturbed podosome-forming rosettes and the resulting extracellular matrix (ECM) degradation in a murine macrophage model depending on core size. This phenomenon was accompanied by a reduction in metalloproteinase MMP2 and an increment in metalloproteinase inhibitors, TIMP-1/2 and SerpinE1. We also found that AuNP treatment has opposite effects on focal adhesions (FA) in endothelial and mesenchymal stem cells. While endothelial cells reduced their mature FA number and ECM degradation rate upon AuNP treatment, mouse mesenchymal stem cells increased the number and size of mature FA and, therefore, the ECM degradation rate. Overall, AuNP appear to disturb adhesive structures and therefore migratory/invasive cell functions measured as ECM degradation ability, providing new insights into AuNP\textendashcell interaction depending on cell type.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}