According to their high electron density and ultrasmall size, gold nanoclusters (AuNCs) have unique luminescence and photoelectrochemical properties that make them very attractive for various biomedical fields. We present an overview of the interaction between ultrasmall luminescent gold nanoclusters and lipidic membranes through electrostatic attraction, showing that it is possible to induce a large change in membrane structures or not. An efficient method was developed to encapsulate them into vesicle for drug delivery. These probes are easily internalized into cells through specific membrane protein targeting and also in vivo organisms.

Here, I will describe my lab’s efforts to improve medicine contrast via customized plasmonic contrast agents and imaging including in vitro and in vivo applications. I will discuss the medical needs and limitations of current technology and then describe how colloidal materials can solve these fundamental limitations. The first example will be imaging and quantitation of reactive oxygen species implicated in a variety of inflammatory disease. The second will be colorimetric sensing of proteases with implications in surveillance of infectious diseases including SARS viruses. I will close with an overview of more fundamental work creating nanoparticles with exotic yet exquisitely controlled shapes and hybrid structures.

The plasmonic photothermal effect involves nonradiative conversion of light to heat by plasmonic nanostructures. It has attracted significant attention due to their widespread potential applications in developing energy conversion devices, therapeutic agents, and sensors and actuators. Here we report our recent progress on the design and preparation of plasmonic nanostructures for photothermal conversion. We first introduce the general principle of plasmonic photothermal conversion and then discuss the strategies for improving efficiency, which has been the focus of this field. We then discuss a number of typical application types, such as solar energy harvesting, steam generation, photothermal actuation, color printing, and therapy to elucidate how to tailor the nanomaterials to meet the requirements of these specific applications.

Glioblastoma is a brain cancer with a five-year survival rate of <5%. MRI and surgical biopsy are typically used to verify the malignancy of a brain tumor, but diagnosis of the aggressive glioblastoma usually occurs at stage IV. Once diagnosed, patients often undergo surgical tumor resection followed by chemotherapy and radiation, which ultimately end in palliative care. There is a current need for a novel theranostic method that allows for early detection and treatment of glioblastoma. Prussian Blue nanoparticles (PBNPs) have been investigated as dual photothermal ablation/photoacoustic imaging agents. Still, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma theranostics is limited. To overcome this, we have developed a way to coat PBNPs with a U-87 extracellular vesicle (EV) layer to allow for increased accumulation within glioblastoma tumors due to EV’s innate passage through the BBB.

Plasmonic nanoparticles are used in many biomedical applications, ranging from sensing to in vivo imaging and photothermal transduction. The tunable morphology of nanostars including metallic composition, spike length, spike sharpness, and overall size greatly impacts their optical and plasmonic properties. Here, we highlight 3 distinct classes of nanostar-based particle groups where the effect of tuning these properties was investigated: improved gold nanostars (GNS), bimetallic nanostars (BNS), and caged nanostars (CNS). After characterization and simulation via FDTD modeling, particles were assessed for their utility in small-molecule detection, gene probe-based plasmonic sensing, in vivo tumor imaging and detection, and photothermal transduction.

Current drug discovery is facing numerous challenges: antimicrobial resistance, increased risk of future pandemics from globalization, spiralling costs of new drugs, etc. High-throughput (HT) synthesis with robotized operations driven by AI algorithms could help to accelerate drug discovery and development, but it requires miniaturized sample volumes. The majority of new drugs entering the market are chiral. Therefore, new experimental tools are needed to probe chirality in tiny volumes. Solving a 40-years old scientific question, our team reported a new chiral optical effect that probes chirality in tiny volumes across a range of inorganic nanoparticles, randomly distributed in isotropic liquids.

SERS nanoparticles are powerful optical contrast agents for imaging assays. Their highly specific sets of narrow spectral bands make them well suited for multiplexing applications, and their enhanced inelastic scattering cross sections enable rapid, high content imaging. Multiplexed hyperspectral imaging datasets commonly undergo a spectral unmixing postprocessing step using a compensation matrix of reference spectra to produce quantitative image channels. We perform hyperspectral Raman imaging on mixtures with increasing plexity and varying degrees of linear system conditioning and compare against the ground truth to determine the most robust workflow for quantitative biological SERS imaging.

Short wave infrared (SWIR) imaging is an emerging imaging modality that utilizes the near infrared-II (NIR-II) biological window, spanning from 1000 nm to 1700 nm. In comparison with traditional NIR-I imaging, SWIR imaging advances with low autofluorescence and superior tissue penetration, leading to high signal-to-noise contrast. In this study, we synthesized multiple PbS/CdS core/shell QDs with distinctive emissions across the whole NIR-II window with high quantum yields and photostability. Empowered by the core/shell QDs, we performed detailed in vivo lymphatic system mapping and multiplexed lymph node imaging that were otherwise unachievable from established NIR-I imaging.

A hollow porous platinum nanostructure was synthesized using a novel silver-micelle combined dual template method. Such nanoparticles enabled photothermal therapy of cancers with near-infrared second window (NIR-II). Because of the unique hollow core and porous shell structure, drastically increased loading capacity was achieved with anti-tumor therapeutics. Furthermore, the high catalysis efficiency of platinum porous shell could effectively catalyze the decomposition of endogenous H2O2 into O2 to relieve the tumorous hypoxia microenvironment and consequently enhance the therapeutic efficiency. Apparently, the hollow porous platinum nanostructures endow the possibility of treating tumors with multimodal imaging-guided NIR-II photothermal therapy in combination with other therapies.

Silver chalcogenide nanoparticles are biocompatible, low cost and straightforward to synthesize. They have quantum dot-like optical properties, which have been used in imaging and therapeutic applications. We have found these nanoparticles to have strong x-ray contrast production, especially for mammography. We have also innovated in their synthesis by developing an ambient conditions, room temperature method, using a microfluidic chip, which results in nanoparticles that have almost complete clearance within 24 hours. Last, encapsulation in a biodegradable polymer matrix results in remarkable enhancement of the optical properties of these nanoparticles, allowing markedly improved optical imaging and photothermal ablation of breast cancer.

In-depth imaging in biology requires the development of bright nonlinear labels (with either fluorescence or frequency conversion properties) which excitation can be done within the transparency window of biological tissues. In this presentation, I will show that, although bulk gold is known to present very low luminescence quantum yield, gold nanorods present a huge 2-photon luminescence with an apparent high influence of the particle volume. After clarifying the role of plasmon in these properties, I will also discuss the interest of taking profit of plasmons to enhance the frequency conversion properties of dielectric nanocrystals.

We report on the use of lipoic acid-appended polyethylene glycol (LA-PEG)-stabilized AuNPs, covalently coupled to dye-labelled peptides, as sensitive optically-addressable sensors for determining the catalytic efficiency of the human matrix metalloproteinase-14 (MMP-14), a cancer biomarker. We exploit real-time dye PL recovery triggered by MMP-14 hydrolysis of the AuNP-tethered peptide-dye to extract quantitative analysis of the proteolysis kinetics. Sub-nanomolar limit of detections for MMP-14 has been achieved using our hybrid bioconjugates.

Quantum dots (QDs) are nanocrystals composed of semiconductors that have been used as probes, sensors, and labels in life sciences research for more than 25 years. Broad adoption of QDs has been impeded by nuances of their colloidal nature, often leading to unreliable measurements in the hands of end users. Coatings contribute to QD colloidal properties and major efforts have aimed to engineer hydrophilic adsorbates that stabilize QDs in aqueous solution while preventing nonspecific binding and steric hindrance that limit applications. This talk will describe the historical development of QD coatings, current challenges, and recent advancements in the field.

Plankton is made of microscopic organisms living in salty or fresh waterish environments. Among these, shelled diatoms microalgae are capable to biomineralize inorganic silicate salts to produce nanostructured silica skeletons known as frustules. Diatom frustules are attractive for material scientists due to their possibility to be used as micro/nano structures useful for building up smart functional nanomaterials. Contrary to industrial silica, biosilica is produced at mild natural conditions. Here we present works about green extraction of biosilica from centric diatom species, chemically decorated with the antioxidant TEMPO radical trap, and used for bursting bone cells growth. Near this, we demonstrated that an in vivo functionalization of diatom biosilica with a bisphosphonate compound, sodium alendronate, leads to a final in vivo decorated and extracted material which exhibited the property of induction of osteoblasts activity and inhibition of osteoclasts proliferation.

This communication addresses new inputs in the field of biosensing, diagnosis and theranostics by using engineered inorganic nanomaterials. We explore the use of gold nanoparticles (AuNPs), SuperParamagnetic Iron Oxide nanoparticles (SPIONs) and SPIONs decorated with AuNPs as new sensing nanoplatforms for cysteine. Another application concerns the targeting of extracellular vesicles. AuNPs are functionalized according to the biomarkers of interest. Raman, UV-Vis, XPS, DLS, zeta potential measurements, combined with SPR and TEM observations highlight grafting and colloidal stability at each step of the synthesis. Developments based on SPIONs as well as titanate nanotubes, as nanotheranostics tools, are also briefly presented.

Copper (Cu) pesticides are aggressively used in the agriculture industry worldwide on many crops. There is an increasing concern of Cu accumulation in field soil, Cu leaching potential into the surrounding ecosystem and development of bacterial resistance. Using nanotechnology, it is possible to reduce Cu amount per application without compromising overall efficacy. Moreover, Zn and Mg based nanomaterials can be developed for potential use as an alternative to Cu bactericides/fungicides. This presentation will focus on laboratory, greenhouse and field efficacy outcome of several nanoparticle composites, challenges towards developing industrially viable formulations and approaches to minimize regulatory challenges.