Aurore Fraix

Bio: Aurore Fraix is an academic researcher from University of Catania. The author has contributed to research in topics: Singlet oxygen & Medicine. The author has an hindex of 20, co-authored 67 publications receiving 1177 citations. Previous affiliations of Aurore Fraix include European University of Brittany & University of Western Brittany.

Photoresponsive polymer nanocarriers with multifunctional cargo

Abstract: Nanoparticles with photoresponsive character can be assembled from amphiphilic macromolecular components and hydrophobic chromophores. In aqueous solutions, the hydrophobic domains of these species associate to produce spontaneously nanosized hosts with multiple photoresponsive guests in their interior. The modularity of this supramolecular approach to nanostructured assemblies permits the co-encapsulation of distinct subsets of guests within the very same host. In turn, the entrapped guests can be designed to interact upon light excitation and exchange electrons, energy or protons. Such photoinduced processes permit the engineering of properties into these supramolecular constructs that would otherwise be impossible to replicate with the separate components. Alternatively, noninteracting guests with distinct functions can be entrapped in these supramolecular containers to ensure multifunctional character. In fact, biocompatible luminescent probes with unique photochemical and photophysical signatures have already emerged from these fascinating investigations. Thus, polymer nanocarriers can become invaluable supramolecular scaffolds for the realization of multifunctional and photoresponsive tools for a diversity of biomedical applications.

Hyaluronan-decorated polymer nanoparticles targeting the CD44 receptor for the combined photo/chemo-therapy of cancer.

Abstract: In the attempt to develop novel concepts in designing targeted nanoparticles for combination therapy of cancer, we propose here CD44-targeted hyaluronan-decorated double-coated nanoparticles (dcNPs) delivering the lipophilic chemotherapeutic docetaxel (DTX) and an anionic porphyrin (TPPS4). dcNPs are based on electrostatic interactions between a negative DTX-loaded nanoscaffold of poly(lactide-co-glycolide), a polycationic shell of polyethyleneimine entangling negatively-charged TPPS4 and finally decorated with hyaluronan (HA) to promote internalization through CD44 receptor-mediated endocytosis. DTX/TPPS4-dcNPs, prepared through layer-by-layer deposition, showed a hydrodynamic diameter of around 180 nm, negative zeta potential and efficient loading of both DTX and TPPS4. DTX/TPPS4-dcNPs were freeze-dried with trehalose giving a powder that could be easily dispersed in different media. Excellent stability of dcNPs in specific salt- and protein-containing media was found. Spectroscopic behavior of DTX/TPPS4-dcNPs demonstrated a face-to-face arrangement of the TPPS4 units in non-photoresponsive H-type aggregates accounting for an extensive aggregation of the porphyrin embedded in the shell. Experiments in MDA-MB-231 cells overexpressing the CD44 receptor demonstrated a 9.4-fold increase in the intracellular level of TPPS4 delivered from dcNPs as compared to free TPPS4. Light-induced death increased tremendously in cells that had been treated with a combination of TPPS4 and DTX delivered through dcNPs as compared with free drugs, presumably due to efficient uptake and co-localization inside the cells. In perspective, the strategy proposed here to target synergistic drug combinations through HA-decorated nanoparticles seems very attractive to improve the specificity and efficacy of cancer treatment.

Combination of PDT photosensitizers with NO photodononors

Abstract: Combination of photodynamic therapy (PDT) with other treatment modalities is emerging as one of the most suitable strategies to increase the effectiveness of therapeutic action on cancer and bacterial diseases and to minimize side effects. This approach aims at exploiting the additive/synergistic effects arising from multiple therapeutic species acting on different mechanistic pathways. The coupling of PDT with photocontrolled release of nitric oxide (NO) through the appropriate assembly of PDT photosensitizers (PSs) and NO photodonors (NOPDs) may open up intriguing avenues towards new and still underexplored multimodal therapies not based on “conventional” drugs but entirely controlled by light stimuli. In this contribution, we present an overview of the most recent advances in this field, illustrating several strategies to assemble PSs and NOPDs allowing them to operate independently without reciprocal interferences and describing the potential applications with particular emphasis on their impact in anticancer and antibacterial research.

Nanotechnology for Multimodal Synergistic Cancer Therapy

Abstract: The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely “1 + 1 > 2”) effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furtherm...

Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy

Abstract: Tumour chemotherapy employs highly cytotoxic chemodrugs, which kill both cancer and normal cells by cellular apoptosis or necrosis non-selectively. Catalysing/triggering the specific chemical reactions only inside tumour tissues can generate abundant and special chemicals and products locally to initiate a series of unique biological and pathologic effects, which may enable tumour-specific theranostic effects to combat cancer without bringing about significant side effects on normal tissues. Nevertheless, chemical reaction-initiated selective tumour therapy strongly depends on the advances in chemistry, materials science, nanotechnology and biomedicine. This emerging cross-disciplinary research area is substantially different from conventional cancer-theranostic modalities in clinics. In response to the fast developments in cancer theranostics based on intratumoural catalytic chemical reactions, this tutorial review summarizes the very-recent research progress in the design and synthesis of representative nanoplatforms with intriguing nanostructures, compositions, physiochemical properties and biological behaviours for versatile catalytic chemical reaction-enabled cancer treatments, mainly by either endogenous tumour microenvironment (TME) triggering or exogenous physical irradiation. These unique intratumoural chemical reactions can be used in tumour-starving therapy, chemodynamic therapy, gas therapy, alleviation of tumour hypoxia, TME-responsive diagnostic imaging and stimuli-responsive drug release, and even externally triggered versatile therapeutics. In particular, the challenges and future developments of such a novel type of cancer-theranostic modality are discussed in detail to understand the future developments and prospects in this research area as far as possible. It is highly expected that this kind of unique tumour-specific therapeutics by triggering specific in situ catalytic chemical reactions inside tumours would provide a novel but efficient methodology for benefiting personalized biomedicine in combating cancer.

Mechanized Silica Nanoparticles: A New Frontier in Theranostic Nanomedicine

Abstract: Medicine can benefit significantly from advances in nanotechnology because nanoscale assemblies promise to improve on previously established therapeutic and diagnostic regimes. Over the past decade, the use of delivery platforms has attracted attention as researchers shift their focus toward new ways to deliver therapeutic and/or diagnostic agents and away from the development of new drug candidates. Metaphorically, the use of delivery platforms in medicine can be viewed as the "bow-and-arrow" approach, where the drugs are the arrows and the delivery vehicles are the bows. Even if one possesses the best arrows that money can buy, they will not be useful if one does not have the appropriate bow to deliver the arrows to their intended location. Currently, many strategies exist for the delivery of bioactive agents within living tissue. Polymers, dendrimers, micelles, vesicles, and nanoparticles have all been investigated for their use as possible delivery vehicles. With the growth of nanomedicine, one can envisage the possibility of fabricating a theranostic vector that could release powerful therapeutics and diagnostic markers simultaneously and selectively to diseased tissue. In our design of more robust theranostic delivery systems, we have focused our attention on using mesoporous silica nanoparticles (SNPs). The payload "cargo" molecules can be stored within this robust domain, which is stable to a wide range of chemical conditions. This stability allows SNPs to be functionalized with stimulus-responsive mechanically interlocked molecules (MIMs) in the shape of bistable rotaxanes and psuedorotaxanes to yield mechanized silica nanoparticles (MSNPs). In this Account, we chronicle the evolution of various MSNPs, which came about as a result of our decade-long collaboration, and discuss advances in the synthesis of novel hybrid SNPs and the various MIMs which have been attached to their surfaces. These MIMs can be designed in such a way that they either change shape or shed off some of their parts in response to a specific stimulus, such as changes in redox potential, alterations in pH, irradiation with light, or the application of an oscillating magnetic field, allowing a theranostic payload to be released from the nanopores to a precise location at the appropiate time. We have also shown that these integrated systems can operate not only within cells, but also in live animals in response to pre-existing biological triggers. Recognizing that the theranostics of the future could offer a fresh approach to the treatment of degenerative diseases including cancer, we aim to start moving out of the chemical domain and into the biological one. Some MSNPs are already being tested in biological systems.