Thibault Gallavardin

Transparent Plasmonic Nanocontainers Protect Organic Fluorophores against Photobleaching

Numerous research efforts are investigating the possibility of using light interactions with metallic nanoparticles to improve the fluorescence properties of nearby molecules. Few investigations have considered the encapsulation of molecules in metallic nanocavities. In this paper, we present the optical properties of new hybrid nanoparticles consisting of gold nanoshells and fluorescent organic dyes in their liquid cores. Microspectroscopy on single nanoparticle demonstrates that the extinction spectra are in good agreement with Mies theory. Finite difference time domain (FDTD) calculations reveal that excitation and emission radiations are efficiently transmitted through the thin gold nanoshells. Thus, they can be considered as transparent plasmonic nanocontainers for photoactive cores. In agreement with FDTD calculations, measurements show that fluorophores encapsulated in gold nanoshells keep their brightness, but they show fluorescence lifetimes 1 order of magnitude shorter. As a salient consequence, the photoresistance of encapsulated organic dyes is also improved by an order of magnitude. This unusual ultraviolet photoresistance results from the reduced probability of triplet-singlet conversion that eventually exposes dyes to singlet oxygen photodegradation.

Biocompatible well-defined chromophore–polymer conjugates for photodynamic therapy and two-photon imaging

A versatile approach is introduced for the synthesis of well-defined, biocompatible conjugates combining two-photon chromophores and hydrophilic multifunctional polymers synthesized by RAFT controlled radical polymerization. As an illustration, two different classes of conjugates carrying multiple fluorophores (based on an anthracene moiety, Anth) or photosensitizers (based on a dibromobenzene moiety, DBB) along the polymer chain were elaborated for bioimaging and photodynamic therapy (PDT) applications, respectively. In both cases, the polymer greatly improved the solubility in biorelevant media as well as the cell uptake. Anth conjugates provided high quality fluorescence microscopy images using both one- and two-photon excitation. DBB conjugates potently induced the death of cancer cells upon photoactivation.

Synthesis, Photophysical Characterization, and Photoinduced Antibacterial Activity of Methylene Blue-loaded Amino- and Mannose-Targeted Mesoporous Silica Nanoparticles

Over the last 20 years, the number of pathogenic multi-resistant microorganisms has grown steadily, which has stimulated the search for new strategies to combat antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based on conventional antibiotics. We have explored the effectiveness of methylene blue-loaded targeted mesoporous silica nanoparticles (MSNP) in the photodynamic inactivation of two Gram negative bacteria, namely Escherichia coli and Pseudomonas aeruginosa. For E. coli, nanoparticle association clearly reduced the dark toxicity of MB while preserving its photoinactivation activity. For P. aeruginosa, a remarkable difference was observed between amino- and mannose-decorated nanoparticles. The details of singlet oxygen production in the nanoparticles have been characterized, revealing the presence of two populations of this cytotoxic species. Strong quenching of singlet oxygen within the nanoparticles is observed.

Influence of bromine substitution pattern on the singlet oxygen generation efficiency of two-photon absorbing chromophores

A molecular engineering strategy based on rational variations of the bromine substitution pattern in two-photon absorbing singlet oxygen sensitizers allows studying the relations that exist between the positioning of an inter-system crossing promoter on the charge-transfer chromophore and its ability to generate singlet oxygen.

Two-photon absorbing chromophores for photodynamic therapy: molecular engineering and in vivo applications

Recent examples of our works in the field of molecular engineering of chromophores for two-photon photodynamic therapy (PDT), and their vectorization into biological medium are presented and discussed. In a first section of this article, we show that a commercial amphiphilic diblock copolymer can be used as a micellar container for efficient delivery of s standard two-photon PDT sensitizer into cells. In a second section, we show how a simple molecular engineering strategy can be used to improve the performances of two-photon PDT sensitizer in the biological transparency-window.

An optimized procedure for direct access to 1H-indazole-3-carboxaldehyde derivatives by nitrosation of indoles

Indazole derivatives are currently drawing more and more attention in medicinal chemistry as kinase inhibitors. 1H-indazole-3-carboxaldehydes are key intermediates to access to a variety of polyfunctionalized 3-substituted indazoles. We report here a general access to this motif, based on the nitrosation of indoles in a slightly acidic environment. These very mild conditions allow the conversion of both electron-rich and electron-deficient indoles into 1H-indazole-3-carboxaldehydes.

Two photon photosensitizers for PDT: molecular engineering towards understanding of their excited state photophysics

We have recently initiated a research project that aims at understanding how systematic variations of the number and positioning of a given Inter-System Crossing (ISC) promoter (1,4-dibromophenyl) along the Intramolecular Charge Transfer (ICT) axis of chromophores will affect the outcome of singlet oxygen production, and how this effect will be related to the nature of the ICT transition. In this communication, this strategy is discussed and we show that a clear influence of the ISC promoter’s position on the chromophore exists, which can be used both to improve the singlet oxygen generation efficiency of the sensitizer, but also its linear and nonlinear spectroscopic features.

Multifunctional hybrid nanoparticles for two-photon fluorescence imaging and photodynamic therapy

We review our work on several strategies to elaborate multifunctional nanoparticules for two-photon imaging or/and photodynamic therapy. Our first strategy is based on the incorporation of two-photon hydrophobic fluorophors in bio-compatible pluronic micelles using the mini-emulsion technique. Our second strategy is based on fluorescent organic nanocrystal grown in silicate spheres. These core-shell hybrid nanoparticles are obtained by a spray-drying process from sol-gel solutions. Our third strategy consists in the encapsulation of hydrophilic molecules in the water core of gold nanospheres. They are obtained by a stabilized emulsion in biphasic liquid-liquid medium without surfactant.