A good comprehension of the parameters influencing the synthesis of gold-pNIPAM core-shell nanoparticles is crucial to preparing well-controlled and scalable protocols with tunable properties. In this work, new insights are provided regarding the crucial role of nucleation points – regardless of gold core sizes – in the fabrication of pNIPAM-encapsulated gold cores by showing their influence on the modulation of key parameters, e.g., encapsulation yield of cores, size, and shrinkage capacity of the hybrid nanomaterial. Moreover, by taking advantage of both the well-controlled protocol and colloidal stability that gold-pNIPAM core-shell nanoparticles offer, photopolymerized thin pNIPAM hydrogel films containing pNIPAM-encapsulated gold cores were fabricated through a simple and squeeze-based method, resulting in homogeneous – in terms of gold core number density – and micron-sized thickness films with tunable optical properties.

Metal nanoparticles (NPs) possess unique physicochemical and optical properties that render them interesting in various applications. Furthermore, it is often advantageous to employ nanostructured assemblies rather than individual NPs because of the modification of their optical properties through plasmon coupling.[1] Combining NPs of different compositions has also proven to be promising for applications in catalysis and sensing.[2] However, the preparation of a low-cost nanostructured material with a high degree of order at a large scale remains challenging.[3] In this context, bottom-up approaches based on self-assembly are attractive, despite their tendency to yield more heterogeneous structures than top-down approaches.[4] The main objective of this project is to investigate the self-assembly of gold (Au), palladium (Pd), and silver (Ag) NPs assisted with a diblock copolymer, the poly(styrene-b-2-vinylpyridine) (PS-b-P2VP). First, NPs of a size between 4 and 15 nm are produced. Then, different populations of hydrophobic NPs are prepared by ligand exchange with alkanethiol of various chain lengths. The NPs mixed with PS-b-P2VP are self-assembled using the Langmuir-Blodgett (LB) technique, a bottom-up approach that allows the transfer of monomolecular films onto glass substrates. A regrowth step[5] is applied to the immobilized NPs to increase their size. The morphology and organization of the nanostructures (NSs) are studied by transmission electron microscopy (TEM). The optical properties of these assemblies are characterized with a UV-visible spectrophotometer. Thermogravimetric analysis confirms that no free ligand remains within the samples after purification by centrifugation and suggests a dense surface coverage of the NPs with alkanethiol ligands. TEM analysis reveals the self-assembly of NPs is limited to NPs under 10-nm diameter. AuNPs covered with octanethiol self-assemble into a circular array of NPs. AgNPs capped with dodecanethiol, and AuNPs and PdNPs both functionalized with octadecanethiol disperse inside the hydrophobic domains formed by the polystyrene chains. The study demonstrates the self-assembly of AuNPs and PdNPs with the LB technique is promising for the development of core-satellite plasmonic NSs. References [1] Liu, D.; Xue, C. Adv. Mater. 2021, 2005738. [2] Choi, H.-K.; Lee, K. S.; Shin, H.-H.; Koo, J.-J.; Yeon, G. J.; Kim, Z. H. Acc. Chem. Res. 2019, 52, 3008−3017. [3] Wei, H; Abtahi, S. M. H.; Vikesland, P. J. Environ. Sci.: Nano 2015, 2, 120-135. [4] Jahn, M.; Patze, S.; Hidi, I. J.; Knipper, R.; Radu, A. I. et al., Analyst 2016, 141, 756-793. [5] Lemineur, J.-F.; Schuermans, S.; Marae-Djouda, J.; Maurer, T.; Ritcey, A. M. J. Phys. Chem. C 2016, 120, 8883−8890.  

The localized surface plasmon resonance (LSPR) phenomenon of coinage metal nanoparticles attracts a great interest in the biosensing field. Gold is often preferred in the majority of LSPR sensing experiments owing to its chemical stability and resistance to oxidation. In this work, synthesis of silver@gold core-shell nanoparticles (Ag@AuNPs) and hollow Au nanoparticles (HAuNPs) with tunable sizes is reported. For Ag@AuNPs, silver nanoparticles (AgNPs) seeds were prepared by Lee and Meisel’s method [1] from mixtures of silver nitrate and sodium citrate. By controlling the amount of citrate solution, 20-60 nm diameter AgNPs could be obtained. The coating of AgNPs with an Au layer was achieved following a two-step reduction [2] with hydroxylamine and HAuCl43H2O. The morphology of Au on AgNPs’ surface could be tuned by adjusting the volumes of hydroxylamine and HAuCl43H2O solutions, starting from discontinuous Au spots to fully covered Au shell. The LSPR band of Ag@AuNPs ranges from 400~600 nm depending on particle size and surface morphology. μ HAuNPs were synthesized through the well-established galvanic replacement reaction using cobalt nanoparticles (CoNPs) as sacrificial templates. In brief, an aqueous solution of cobalt chloride and sodium citrate was degassed by bubbling nitrogen for 1 h. Then a mixture of freshly prepared sodium borohydride and borate was injected into the solution under nitrogen protection. The size of CoNPs could be tuned from 15 to 80 nm by adjusting the amount of borate [3]. The galvanic exchange was conducted by quickly pouring CoNPs solution into a deaerated solution of HAuCl43H2O with vigorous stirring in a glove box. Lastly, the colloids were exposed to ambient conditions allowing the cobalt core to be oxidised. The shell thickness of HAuNPs is dependent on the concentration of HAuCl4 and ranges from 10% to 30% of the outer radius. Regarding their optical properties, the two sets of nanoparticles displayed strong and tunable LSPR bands in the visible range ranging from 500 to 800 nm and the position of their plasmon bands is independent of the pH of the surrounding medium. Therefore, Ag@AuNPs and HAuNPs show a great potential for LSPR biosensing.

Metallic nanoparticles have unique physicochemical and optical characteristics which make them interesting for use in many fields. The assembly of individual nanoparticles into organised nanostructures leads to interparticle coupling that significantly modifies the plasmonic properties. Previous work in our laboratory demonstrated that gold nanoparticles can be conveniently assembled into ring structures within Langmuir-Blodgett films of a block copolymer template. Unfortunately, all attempts to exploit the same strategy to obtain analogous assemblies of silver nanoparticles failed. The objective of the present study is to obtain silver nanostructures through the growth of a silver layer on pre-organized gold seeds. Silver is very attractive for many applications because it presents the highest plasmonic efficiency and strongest plasmonic extinction among the noble metals. First, 5 nm gold nanoparticles are synthesized using the Brust-Schiffrin method and then functionalized with 1-octanethiol. The gold particles are assembled into nano-ring structures within a poly(styrene-b-2-vinylpyridine) matrix spread at the air-water interface [1]. The films are then transferred to a glass substrate by the Langmuir-Blodgett technique. Metallic silver is deposited on the gold seeds by placing the samples in a silver nitrate solution at various concentrations, temperatures and reaction times. A reducing agent such as L-ascorbic acid, sodium citrate or hydroquinone is also added to form the silver layer on the gold seeds. These new assemblies are analyzed by transmission electron microscopy and UV-visible spectroscopy. The hybrid structures exhibit two extinction maxima, at around 410 and 550 nm, corresponding to the plasmon frequencies of silver and gold plasmon, respectively. Depending on the exact conditions, it is possible to grow silver nanoparticles with diameters of 15 to 40 nm on the prearranged gold seeds using L-ascorbic acid, sodium citrate or hydroquinone as a reductant. Silver growth, however, is not restricted to the gold seeds and further research will focus on identifying more selective reduction conditions.

Remarkable optical properties of gold nanorods are assigned to collective oscillation of valence band electrons of metal nanoparticles, known as surface plasmon resonance (SPR). Widely studied linear and nonlinear optical properties of gold nanostructures were utilized in catalysis, imaging, sensing, photothermal therapy and in a broad sense theranostics applications.[1] Therefore, plasmonic nanoparticles are found as a universal material for applications in complexed systems, including detection of fluorescent species. Gold nanorods are well-known from narrow size distribution and well-established structure that lead to uniform optical properties, essential for systematic investigation of single molecule and single-nanoparticle interaction. With tuneable surface plasmon resonance they can be easily adjusted for desirable application. Moreover, anisotropic plasmonic nanoparticles induce strong local electric field at the sharp tips, that are easily reachable for chromophores floating nearby the nanoparticle. In this approach amplification of electric field at the tips of nanorods lead to enhanced luminescence of weakly emitting molecules. Plasmon enhanced luminescence of chromophores was in majority examined with common quantum dots, fluorescent dyes or fluorescent proteins. The literature provide detailed description of experimental requirements for strong luminescence enhancement in the near proximity of AuNRs.[2] Crucial role of nanorod-assisted luminescence enhancement is selection of nanorods that present spectral overlap of SPR band and emission spectrum of analysed fluorophores. Although recent findings provide various single-molecule studies of plasmon-enhanced luminescence detection of fluorophores under one-photon excitation, [3] the multiphoton study are still poorly investigated in this field.[4] Compared to one-photon study, two-photon excitation is known from deeper penetration into biological samples, higher axial resolution and better signal to noise ratio, therefore it is preferred in bioimaging applications. Besides, higher order of processes benefit to stronger enhanced responses, in particular in plasmonic excitation. In this work atomically-precise Au18(SG)14 nanoclusters were examined under one- and two-photon excitation. Their strong emission is located near infrared (NIR), the most attractive region in terms of bioimaging applications. However, their relatively low quantum yield of approximately 5% is challenging for imaging of single nanoclusters using standard imaging techniques. Gold nanorod-assisted technique of luminescence enhancement of Au18(SG)14 was proposed in order to achieve single molecule sensitivity of detection. [5] The aim of this work was to monitor photoluminescence of single AuNCs diffusing in the close vicinity of plasmonic nanoparticles. One-photon optical properties of Au18 NCs were determined, which were further systematically investigated in nonlinear regime. Resulting 25-fold enhancement of two-photon luminescence of nanoclusters is related to resonant excitation of plasmonic nanorods. Strong two-photon enhancement of weakly emissive atomically-precise nanoclusters is monitored for the first time in this field. The preliminary study of single nanocluster – single plasmonic nanoparticle interactions brings new possibilities for plasmonically enhanced gold nanoclusters applications in single particle sensing and imaging. References [1] Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A., Nanomedicine 2007, 2 (5), 681-693. [2] Abadeer, N. S.; Brennan, M. R.; Wilson, W. L.; Murphy, C. J., ACS Nano 2014, 8 (8), 8392-8406. [3] Khatua, S.; Paulo, P. M. R.; Yuan, H.; Gupta, A.; Zijlstra, P.; Orrit, M., ACS Nano 2014, 8 (5), 4440-4449. [4] Zhang, W.; Caldarola, M.; Lu, X.; Orrit, M., ACS Photonics 2018, 5 (7), 2960-2968 [5] Pniakowska, A.; Olesiak-Banska, J. Molecules 2022, 27, 807

Metal sulfide materials have been considered as a growing class of ion exchangers that have drawn more and more attention in adsorption areas in virtue of their interesting properties. Fe3S4 (Greigite) and Fe7S8 (Pyrrhotite), are two abundant iron sulfide materials in nature, have unique magnetism and fascinating reactive functional groups, these properties make them promising adsorbents for many adsorption areas, and they have been proved to be able to adsorb or remove many hazardous species in the last few years. Theoretically, iron sulfide materials are also very promising for gold recovery, however, as far as we know, there is no report to use iron sulfide materials in gold recovery. In this work, iron sulfide materials were applied in gold recovery for the first time. Four iron sulfide materials were fabricated using hydrothermal or solvothermal methods. During the adsorption, gold chloride ions were reduced to metallic gold on each of the iron sulfide materials, however, the four materials showed different capacities and magnetism after gold recovery. One of the materials achieved a high gold loading capacity (2161 mg/g) and remain magnetic with loaded gold. Various characterizations revealed that the four materials have different morphologies, compositions, and crystal structures. This study not only presented a simple method of fabricating an ultraefficient, magnetic, and recyclable adsorbent for gold recovery, but also investigated the mechanism of the reduction of gold on iron sulfides.

Manganese, iron and cobalt oxides were supported on TiO2 by deposition-precipitation with urea method then gold nanoparticles were added as a second active phase. The catalysts were evaluated for soot combustion and CO oxidation to elucidate the individual and combined effect of both supported phases. The physicochemical characterization revealed that Mn, Fe and Co were in the form of oxides while Au was in metallic state. The catalytic evaluation for the soot combustion reaction showed a remarkable increase in the activity when the transition metal phase was dispersed on TiO2. It is noteworthy that the performance of the MnOx/TiO2 and CoOx/TiO2 catalysts was superior because they exhibited higher lattice oxygen mobility than the FeOx/TiO2 catalyst, while the effect of Au nanoparticles was to increase selectivity towards CO2. On the other hand, for the CO oxidation, Au active sites were essential and played an important role in carrying out the reaction at lower temperatures. The remarkable activity in the Au-CoOx/TiO2 and Au-FeOx/TiO2 catalysts suggests a promoting effect caused by the combination of the transition metal oxides and Au nanoparticles which helped create new adsorption sites at Au-MOx interfaces for the adsorption and activation of O2 molecules.

Gold nanoparticles (Au NPs) were deposited on cation- and anion-substituted hydroxyapatites (sHAPs). All Au/sHAPs showed oxidative strong metal-support interaction (SMSI), where thin layer of sHAP partly covered Au NPs under an oxidative atmosphere at 300 °C. In Au/sHAP_500_O2 calcined at 500 °C, Au NPs were almost completely encapsulated by the sHAP layer. Catalytic performance of Au/sHAPs_300_O2 (with SMSI) and Au/sHAPs_300_H2 (without SMSI) was examined for oxidative esterification of octanal with ethanol to give ethyl octanoate. Au/sHAPs_300_O2 with SMSI exhibited much higher catalytic activity than did the corresponding Au/sHAPs_300_H2 without SMSI despite the fact that the active surface Au atoms decreased by SMSI. The catalytic activities of Au/sHAP_500_O2 decreased slightly compared with those of Au/sHAP_300_O2 but exhibited still higher activity than did Au/sHAP_300_H2. It implies that the surface Au atoms are still accessible even though the Au NPs were encapsulated by the sHAP layer. It is likely that the increase in the area of the contact structure between the Au surface and sHAP by coverage of the Au NPs with a thin sHAP layer itself contributes to the much improved catalytic activity.

Background. Eye drops represent 90% of all ophthalmic treatments currently used. There is only 0.02% of eye drops therapeutic molecules that reach the eye anterior chamber despite their high concentration. The tear film efficiently protects the cornea, reducing access to the target. Thereby, the increase of the drug bioavailability and efficiency must come from the mucoadhesion optimization of the drug delivery system. The research team of the laboratory already developed and patented a gold nanoparticle synthesis that produce gold nanoparticles presenting ultrastable and mucoadhesive properties. Objectives. The goal was thus to study the gold nanoparticles’ ability to release two specific ophthalmic drugs, flurbiprofen and ketorolac. Parameters of interest were loading parameters, like the ratio of gold nanoparticles to molecules of drug, the loading time, and the intrinsic nature of the two molecules of interest, but also the delivery parameters. The active molecules, ketorolac and flurbiprofen, are two nonsteroidal anti-inflammatory drugs, typically used in post-chirurgical cataract treatments that could truly benefit the use of a vector. Methods. Drug loading kinetics were measured using UV-visible spectroscopy to determine optimal loading parameters. Plasmon bands first derivatives analysis were possible because of the localized surface plasmon resonance effect of the gold core. The drug release was measured using an in vitro model based on dialysis bags coupled with UV-visible spectroscopy. The dialysate was changed throughout time to mimic the dynamic environment of the tear film. Results and discussion. Two saturating points appeared during the drug loading kinetics measurements for the two therapeutic molecules, displaying the gold nanoparticles loading ability with both molecules. However, during release studies, drug delivery percentages showed similar percentages for the two loading-time, suggesting that the second saturating point comes from molecules reorganization inside the polymeric crown instead of a two-step loading mechanism. Drug delivery percentages were higher for hydrophile molecules than hydrophobic molecules. Gold nanoparticles showed to release molecules consistently as the same final released drug percentages were obtained for all gold nanoparticles to drug ratios. Also, a dynamic environment, translated by dialysate changes, induced higher released concentrations. Further experiments with varying conditions will be vital to better understand the impact of the delivery environment on the amount of drug molecules being released. Conclusion. Based on these preliminary results, gold nanoparticles are a promising drug delivery system for ketorolac and flurbiprofen. This nanotechnology demonstrated its drug loading and release abilities with hydrophobic and hydrophile anti-inflammatory drugs. Further experimentations are needed to fully showcase the impact of experimental parameters on drug administration tuning and the potential of gold nanoparticles to improve the medication in ophthalmology.

In this study, gold nanoparticles are synthesized and functionalized with biocompatible hydrophobic polymers and encapsulated into polymeric micelles. Instead of simple functionalization, this approach will allow us to change more variables and explore the unique features of polymeric micelles, such as long blood circulation, different sizes, morphologies as the ability to use different self-assembly techniques and encapsulation methodologies. In addition, it will be possible to co-encapsulate chemotherapeutic drugs and the system will be accessed as not only for diagnostics, but also for treatment, creating a theranostic platform.

Background & Objectives: Eye drops account for 90% of all ophthalmic formulations currently used in treatments [1]. Despite the high drug content of eye drops, a large proportion is eliminated through the tear film, efficiently protecting the cornea and reducing access to the target. Indeed, only 0.02% of the therapeutic molecules in eye drops reach the eye anterior chamber [2]. Thereby, a new mucoadhesive drug delivery system based on ultrastable and non-toxic gold nanoparticles (AuNPs) has been developed to increase the drug bioavailability when administered by eye drops and reduce their administration frequency [2,3]. These nanoparticles can adhere to the mucoid layer of the corneal surface and thus increase the residence time of encapsulated drugs on the eye surface. Increasing corneal residence time is a major pharmacological challenge for the treatment of ocular diseases and injuries. For patients, this nanotechnology could help overcome this challenge because it has the potential to make ophthalmic treatments more effective and tolerable, but also to reduce the side effects of therapeutic molecules and additives, as well as the associated cost. In ophthalmology, corneal wounds account for 37% of all visual disabilities and 23% of medical consultations for ocular problems in North America. Recently, a study showed that the use of the pharmacological inhibitor of the AKT signaling pathway (C646) in combination with the CREB pathway agonist (SC79) accelerated the corneal wound healing in human tissue-engineered corneas as well as in rabbit corneas [4]. The original idea is therefore to combine these innovations, i.e. the encapsulation of these drugs in AuNPs, to significantly improve the corneal wound closure. Methods & Results: PEG-modified AuNPs are synthesized and then fully characterized by various physicochemical techniques. Drug loading kinetics is then measured using UV-visible spectroscopy to determine optimal loading parameters before performing cytotoxicity, 3D in vitro and in vivo studies of AuNPs-encapsulated drugs on corneal wound healing. This valorization project mainly consists in accumulating convincing in vivo data related to the increase of corneal drug residence time by mucoadhesive AuNPs, to the biodistribution of AuNPs in different regions of the ocular system in rabbits, as well as to the drug efficiency on the corneal surface, confirming more specifically the potential of accelerating corneal healing in rabbits with the synergistic combination C646-SC79. Conclusion: The synthesis of ultrastable, mucoadhesive and non-toxic PEG-modified AuNPs is demonstrated and the next challenge of this work is to highlight that mucoadhesive AuNPs are able to improve corneal wound healing by significantly improving the residence time of C646-SC79 therapeutic molecules. [1] Gaudana, R. et al., The AAPS Journal, 2010, 12 (3), 348-360. [2] Ouellette, M. et al., Scientific Reports, 2018, 8 (1), 1-15. [3] Masse, F. et al., Molecules, 2019, 24 (16), 2929. [4] Couture, C. et al., Acta Biomaterialia, 2018, 73: 312-325.

The brain still holds many secrets nowadays in regard to the transfer of information between neurons and how neuro-degenerative diseases affect such functions. Neurotransmitter sensing in the brain is thus crucial for the understanding of neuro-degenerative diseases. By allowing more data to be gathered from the neurotransmission process directly in the brain, neuroscientists could formulate an explanation of neuro-degenerative diseases that could lead to a solution for such diseases or a cure for the symptoms. Most modern methods for detecting neurotransmitters at the synaptic junction rely on bulky instruments or are disruptive to the medium, and are therefore not suitable for such a delicate medium as the brain. In this work, a novel, compact and non-invasive instrument for neurotransmitter detection based on a colorimetric sensing method is described. The colorimetric approach uses specific gold nanoparticles as the detection vector. Ultrastable gold nanoparticles were synthesized and functionalized using neurotransmitter specific aptamers, increasing the sensitivity and selectivity of the interaction between the nanoparticle and the neurotransmitters of interest. From such interaction, the plasmonic resonance band of the gold nanoparticles shifts as a function of the concentration of the neurotransmitter of interest. The measurement of this wavelength shift in time at the synaptic junction level will lead to the monitoring of the neurotransmission process. An instrument was designed to allow the measurement of the wavelength shift. The instrument was designed using a grism diffractive component as opposed to the traditional spectrometer layout in the aim of reducing the physical footprint of the system. Combined with the optical sub-system, a microfluidic sub-system was designed to manipulate the sample in and out of the instrument as well as mix the gold nanoparticles in the solution to make them interact with the neurotransmitters from the sample. Additionally, a micro-electronic sub-system was implemented to manage the other sub-systems as well as gather and analyze data coming from the optical sub-system. A system prototype was assembled in our laboratory and was tested using different gold nanoparticle samples. From those samples, the system presented a resolution of the order of 1 nm, which is the required resolution for the measurement of the wavelength shift of functionalized gold nanoparticles in the presence of the neurotransmitter of interest. The system was also able to gather data semi-autonomously as well as analyze the gathered data to detect the absorbance peak of the solution. At this stage, the prototype presents the properties required for the detection of neurotransmitters using functionalized ultrastable gold nanoparticles and optimization tests are still ongoing. With more testing, the characteristics of the functionalization of the nanoparticles can be tuned iteratively to increase their selectivity and sensitivity while maintaining their properties. Moreover, a new version of the sensing system that aims at reducing the physical footprint while keeping the resolution stable is also being designed.

Culture-based diagnosis of bacterial diseases is a time-consuming technique that can lead to antibiotic resistance or bacteria mutation. In this work, a high-resolution device capable to detect the presence of bacteria based on its dynamics provided by nanoplasmonic markers is presented. As a proof of concept, 100 nm gold nanoparticles were used as biomarkers targeting Escherichia coli (E. coli). The implementation of the nanoplasmonic markers in combination with side-illumination can be coupled with a light reflectance microscope resulting in a high-resolution and -NA instrument able to detect bacteria based on its dynamics.

SERS spectroscopy applied with microfluidic devices and deep learning algorithms allows accurate detection of biological mixtures of related chemical species in a relatively short measurement time. The present project aims to evaluate the potential of SERS spectroscopy combined with a polydimethylsiloxane (PDMS)-based microfluidic device and a convolutional Neural Network (CNN) deep learning model to differentiate and classify different species of bile acids (BA), a large family of molecules with closely related structures. These molecules were selected as they have distinct pathological roles and are currently considered as potential markers of gut barrier permeability. After training and optimizing the model in parallel with spectral preprocessing and data augmentation techniques, the CNN model successfully classified (98.1 ± 0.6) %. The robustness of the CNN predictions was also confirmed on individual BA solutions at different concentrations, as well as on dynamic conditions with a custom microfluidic device.