Molecular-Based Fluorescent Nanoparticles Built from Dedicated Dipolar Thienothiophene Dyes as Ultra-Bright Green to NIR Nanoemitters

Abstract

Fluorescent Organic Nanoparticles (FONs), prepared by self-aggregation of dedicated dyes in water, represent a promising green alternative to the toxic quantum dots (QDs) for bioimaging purposes. In the present paper, we describe the synthesis and photophysical properties of new dipolar push-pull derivatives built from thieno[3,2-b]thiophene as a π-conjugated bridge that connects a triphenylamine moiety bearing various bulky substituents as electron-releasing moiety to acceptor end-groups of increasing strength (i.e., aldehyde, dicyanovinyl and diethylthiobarbiturate). All dyes display fluorescence properties in chloroform, which shifts from the green to the NIR range depending on the molecular polarization (i.e., strength of the end-groups) as well as a large two-photon absorption (TPA) band response in the biological spectral window (700-1000 nm). The TPA bands show a bathochromic shift and hyperchromic effect with increasing polarization of the dyes with maximum TPA cross-section reaching 2000 GM for small size chromophore. All dyes are found to form stable and deeply colored nanoparticles (20-45 nm in diameter) upon nanoprecipitation in water. Although their fluorescence is strongly reduced upon aggregation, all nanoparticles show large one-photon (up to 10 8 M −1 ·cm −1 in the visible region) and two-photon (up to 10 6 GM in the NIR) brightness. Interestingly, both linear and non-linear optical properties are significantly affected by interchromophoric interactions, which are promoted by the molecular confinement and modulated by both the dipolar strength and the presence of the bulky groups. Finally, we exploited the photophysical properties of the FONs to design optimized core-shell nanoparticles built from a pair of complementary dipolar dyes that promotes an efficient core-to-shell FRET process. The resulting molecular-based core-shell nanoparticles combine large two-photon absorption and enhanced emission both located in the NIR spectral region, thanks to a major amplification (by a factor of 20) of the core fluorescence quantum yield. These novel nanoparticles, which combine huge one-and two-photon brightness, hold major promise for in vivo optical bioimaging.

A Bottom‐Up Approach to Red‐Emitting Molecular‐Based Nanoparticles with Natural Stealth Properties and their Use for Single‐Particle Tracking Deep in Brain Tissue

“…[ 8 ] These founding results unveiled the promise that operating confinement‐enhanced dipolar interactions and polarization effects can tune the luminescence properties, colloidal stability, and, most attractively, surface properties of FONs. [ 8,9 ] In this regard, a critical challenge specific to biomedical applications is to control the interactions between NPs and cells. [ 2,10 ] When subcellular compartments are to be targeted (e.g., for drug delivery), fluorescent nanoprobes should penetrate inside the cells.…”

Multimodal optical contrast agents as new tools for monitoring and tuning nanoemulsion internalisation into cancer cells. From live cell imaging to in vivo imaging of tumours

“…1). This type of hemicyanine dye is anticipated to show strong absorption in the visible region and uorescence emission in the far-red to NIR region, 3,16 in relation to an intramolecular charge transfer (ICT) transition from the donor to the acceptor upon excitation. For this same reason, such dyes were expected to display large two-photon absorption cross-sections (s 2 ) in the rst biologically transparent window, i.e., 700-1000 nm, 16,17 as well as large quadratic hyperpolarizability b.…”

“…This type of hemicyanine dye is anticipated to show strong absorption in the visible region and uorescence emission in the far-red to NIR region, 3,16 in relation to an intramolecular charge transfer (ICT) transition from the donor to the acceptor upon excitation. For this same reason, such dyes were expected to display large two-photon absorption cross-sections (s 2 ) in the rst biologically transparent window, i.e., 700-1000 nm, 16,17 as well as large quadratic hyperpolarizability b. 18 Thanks to the presence of the two alkyl (nBu) chains on the terminal nitrogen and of the positively charged opposite acceptor end-group (pyridinium or quinolinium moieties), the hemicyanine dyes show amphiphilic features which were meant to bestow them high affinity for the lipid corona of NEs.…”

Enantiopure polythiophene nanoparticles. Chirality dependence of cellular uptake, intracellular distribution and antimicrobial activity

“…We notice that S and R polymer solutions have similar QY that, as expected, sensibly drop when NPs are formed, in agreement with what has already been observed for uorescent organic nanoparticles (FONs). 35 Nevertheless, despite the low quantum yield, the uorescence intensity of the nanoparticles remains sufficiently high inside living cells (see gures below) owing to the large optical absorption of the conjugated polymers. 36 Fig.…”