Enhanced CRISPR-Cas9 RNA system delivery using cell penetrating peptides-based nanoparticles for efficient in vitro and in vivo applications.

CRISPR-Cas9 system has emerged as a revolutionary gene-editing tool with huge therapeutic potential for addressing the underlying genetic causes of various diseases, including cancer. However, there are challenges such as the delivery method that must be overcome for its clinical application. In addition to the risk of nuclease degradation and rapid clearance of the CRISPR-Cas9 system by macrophages, the large size of Cas9, the high anionic charge density and hydrophilic nature of the RNA hinder their intracellular delivery and overall gene transfection efficiency.

Gold Nanoclusters as High Resolution NIR-II Theranostic Agents.

In the realm of nanomaterials, atomically precise quasi-molecular gold nanoclusters (AuNCs) play a prime role due to their unique, stable, and highly tunable optical properties. They are extensively structure-engineered for modulation of surface electronic states toward long wavelength photoluminescence, particularly in the NIR-II (1000 to 1700 nm) window. Contrast agents with NIR-II emission can potentially transform optical imaging in terms of higher spatial resolution, deeper tissue penetration, and reduced tissue autofluorescence.

Engineering Radiocatalytic Nanoliposomes with Hydrophobic Gold Nanoclusters for Radiotherapy Enhancement.

Chemoradiation therapy is on the forefront of pancreatic cancer care, and there is a continued effort to improve its safety and efficacy. Liposomes are widely used to improve chemotherapy safety, and may accurately deliver high-Z element- radiocatalytic nanomaterials to cancer tissues. In this study, the interaction between X-rays and long-circulating nanoliposome formulations loaded with gold nanoclusters is explored in the context of oxaliplatin chemotherapy for desmoplastic pancreatic cancer.

Expanding the Palette of SWIR Emitting Nanoparticles Based on Au Nanoclusters for Single-Particle Tracking Microscopy.

Single-molecule localization microscopy has proved promising to unravel the dynamics and molecular architecture of thin biological samples down to nanoscales. For applications in complex, thick biological tissues shifting single-particle emission wavelengths to the shortwave infrared (SWIR also called NIR II) region between 900 to 2100 nm, where biological tissues are more transparent is key. To date, mainly single-walled carbon nanotubes (SWCNTs) enable such applications, but they are inherently 1D objects.

Real-time visualization of dextran extravasation in intermittent hypoxia mice using noninvasive SWIR imaging.

Imaging tools are crucial for studying the vascular network and its barrier function in various physiopathological conditions. Shortwave infrared (SWIR) window optical imaging allows noninvasive, in-depth exploration. We applied SWIR imaging, combined with vessel segmentation and deep learning analyses, to study real-time dextran probe extravasation in mice experiencing intermittent hypoxia (IH)-a characteristic of obstructive sleep apnea associated with potential cardiovascular alterations due to early vascular permeability.

Intracellular accumulation and immunological response of NIR-II polymeric nanoparticles.

Polymeric nanoparticles (NPs) are extremely promising for theranostic applications. However, their interest depends largely on their interactions with immune system, including the capacity to activate inflammation after their capture by macrophages. In the present study, we generated monodisperse poly(ethyl methacrylate) (PEMA) NPs loaded with hydrophobic photoluminescent gold nanoclusters (Au NCs) emitting in the NIR-II optical windows and studied their interaction in vitro with J774.

Engineering Liganded Gold Nanoclusters as Efficient Theranostic Agents for Cancer Applications.

Luminescent gold nanoclusters are rapidly gaining attention as efficient theranostic targets for imaging and therapeutics. Indeed, their ease of synthesis, their tunable optical properties and tumor targeting make them potential candidates for sensitive diagnosis and efficacious therapeutic applications. This concept highlights the key components for designing gold nanoclusters as efficient theranostics focusing on application in the field of oncology.

Lipoprotein interactions with water-soluble NIR-II emitting aza-BODIPYs boost the fluorescence signal and favor selective tumor targeting.

Following intravenous administration, the interaction of fluorescent exogenous molecules with circulating endogenous transporters can influence their photophysical properties as well as their fate and distribution, and possibly their recognition by different cell types. This type of interaction can be used to optimize the drug delivery but also the imaging properties of a compound of interest. In this study, we investigated the behavior of SWIR-WAZABY-01 fluorophore, a water-soluble aza-BODIPY dye emitting in the NIR-II region, both and .

Protein-coated nanoparticles exhibit Lévy flights on a suspended lipid bilayer.

Lateral diffusion of nano-objects on lipid membranes is a crucial process in cell biology. Recent studies indicate that nanoparticle lateral diffusion is affected by the presence of membrane proteins and deviates from Brownian motion. Gold nanoparticles (Au NPs) stabilized by short thiol ligands were dispersed near a free-standing bilayer formed in a 3D microfluidic chip.

Lethal Interactions of Atomically Precise Gold Nanoclusters and and Bacterial Cells.

Ultrasmall metal nanoclusters (NCs) are employed in an array of diagnostic and therapeutic applications due to their tunable photoluminescence, high biocompatibility, polyvalent effect, ease of modification, and photothermal stability. However, gold nanoclusters' (AuNCs') intrinsically antimicrobial properties remain poorly explored and are not well understood. Here, we share an insight into the antimicrobial action of atomically precise AuNCs based on their ability to passively translocate across the bacterial membrane.

Tailoring the NIR-II Photoluminescence of Single Thiolated Au Nanoclusters by Selective Binding to Proteins.

Atomically precise gold nanoclusters are a fascinating class of nanomaterials that exhibit molecule-like properties and have outstanding photoluminescence (PL). Their ultrasmall size, molecular chemistry, and biocompatibility make them extremely appealing for selective biomolecule labeling in investigations of biological mechanisms at the cellular and anatomical levels. In this work, we report a simple route to incorporate a preformed Au nanocluster into a model bovine serum albumin (BSA) protein.

Tailoring the SWIR emission of gold nanoclusters by surface ligand rigidification and their application in 3D bioimaging.

The influence of solvent polarity and surface ligand rigidification on the SWIR emission profile of gold nanoclusters with an anistropic surface was investigated. A strong enhancement of the SWIR emission band at 1200 nm was observed when measuring in different local environments: in solution, in polymer composites, and in solids. SWIR imaging of mice assisted by deep learning after intravenous administration of these gold nanoclusters provides high definition pseudo-3D views of vascular blood vessels.

Protein corona modulates interaction of spiky nanoparticles with lipid bilayers.

The impact of protein corona on the interactions of nanoparticles (NPs) with cells remains an open question. This question is particularly relevant to NPs which sizes, ranging from tens to hundreds nanometers, are comparable to the sizes of most abundant proteins in plasma. Protein sizes match with typical thickness of various coatings and ligands layers, usually present at the surfaces of larger NPs.

Deep learning: step forward to high-resolution in vivo shortwave infrared imaging.

Shortwave infrared window (SWIR: 1000-1700 nm) represents a major improvement compared to the NIR-I region (700-900 nm) in terms of temporal and spatial resolutions in depths down to 4 mm. SWIR is a fast and cheap alternative to more precise methods such as X-ray and opto-acoustic imaging. Main obstacles in SWIR imaging are the noise and scattering from tissues and skin that reduce the precision of the method.

Antibacterial Action of Nanoparticles by Lethal Stretching of Bacterial Cell Membranes.

It is commonly accepted that nanoparticles (NPs) can kill bacteria; however, the mechanism of antimicrobial action remains obscure for large NPs that cannot translocate the bacterial cell wall. It is demonstrated that the increase in membrane tension caused by the adsorption of NPs is responsible for mechanical deformation, leading to cell rupture and death. A biophysical model of the NP-membrane interactions is presented which suggests that adsorbed NPs cause membrane stretching and squeezing.

Mechano-Bactericidal Titanium Surfaces for Bone Tissue Engineering.

Despite advances in the development of bone substitutes and strict aseptic procedures, the majority of failures in bone grafting surgery are related to nosocomial infections. Development of biomaterials combining both osteogenic and antibiotic activity is, therefore, a crucial public health issue. Herein, two types of intrinsically bactericidal titanium supports were fabricated by using commercially scalable techniques: plasma etching or hydrothermal treatment, which display two separate mechanisms of mechano-bactericidal action.

Optimization of spatial resolution and scattering effects for biomedical fluorescence imaging by using sub-regions of the shortwave infrared spectrum.

We evaluated the impact of light-scattering effects on spatial resolution in different shortwave infrared (SWIR) sub-regions by analyzing two SWIR emissive phantoms made of polydimethylsiloxane (PDMS)-gold nanoclusters (Au NCs) composite covered with mice skin, or capillary tubes filled with Au NCs or IRDye 800CW at different depth in intralipids and finally, after administration of the Au NCs intravenously in mice. Our findings highlighted the benefit of working at the highest tested spectral range of the SWIR region with a 50% enhancement of spatial resolution measured in artificial model when moving from NIR-II (1000-1300 nm) to NIR-IIa (1300-1450 nm) region, and a 25% reduction of the scattering from the skin determined by point spread function analysis from the NIR-II to NIR-IIb region (1500-1700 nm). We also confirmed that a series of Monte Carlo restoration of images significantly improved the spatial resolution in vivo in mice in deep tissues both in the NIR-II and NIR-IIa spectral windows.

Water-Soluble Aza-BODIPYs: Biocompatible Organic Dyes for High Contrast NIR-II Imaging.

A simple NIR-II emitting water-soluble system has been developed and applied and . , the fluorophore quickly accumulated in 2D and 3D cell cultures and rapidly reached the tumor in rodents, showing high NIR-II contrast for up to 1 week. This very efficient probe possesses all the qualities necessary for translation to the clinic as well as for the development of NIR-II emitting materials.

High-Resolution Shortwave Infrared Imaging of Vascular Disorders Using Gold Nanoclusters.

We synthesized a generation of water-soluble, atomically precise gold nanoclusters (Au NCs) with anisotropic surface containing a short dithiol pegylated chain (AuMHA/TDT). The AuMHA/TDT exhibit a high brightness (QY ∼ 6%) in the shortwave infrared (SWIR) spectrum with a detection above 1250 nm. Furthermore, they show an extended half-life in blood ( = 19.

Surface functionalization of gold nanoclusters with arginine: a trade-off between microtumor uptake and radiotherapy enhancement.

Ultra-small gold nanoclusters (AuNCs) are increasingly investigated for cancer imaging and radiotherapy enhancement. While fine-tuning the AuNC surface chemistry can optimize their pharmacokinetics, its effects on radiotherapy enhancement remain largely unexplored. This study demonstrates that optimizing the surface chemistry of AuNCs for increased tumor uptake can significantly affect its potential to augment radiotherapy outcomes.

Gold nanoclusters for biomedical applications: toward in vivo studies.

In parallel with the rapidly growing and widespread use of nanomedicine in the clinic, we are also witnessing the development of so-called theranostic agents that combine diagnostic and therapeutic properties. Among them, ultra-small gold nanoclusters (Au NCs) show promising potential due to their optical properties and activatable therapeutic activities under irradiation. Furthermore, due to their hydrodynamic diameter of smaller than 6 nm and unique biophysical properties, they also present intriguing behaviors in biological and physio-pathological environments.

Augmented interaction of multivalent arginine coated gold nanoclusters with lipid membranes and cells.

A library of ultra-small red photoluminescent gold nanoclusters (Au NCs) were synthesized with an increasing amount of positive charges provided by the addition of mono-, di- or trivalent-glutathione modified arginine peptides. We then studied how the arginine content impacted on the interaction of Au NCs with negatively charged artificial lipid bilayers and cell membranes. Results indicated that increasing the arginine content enhanced Au NCs' adsorption on lipid bilayers and on cell membranes followed by an increased cellular uptake in melanoma cells (COLO 829).

Ligand shell size effects on one- and two-photon excitation fluorescence of zwitterion functionalized gold nanoclusters.

Gold nanoclusters (Au NCs) are an emerging class of luminescent nanomaterials but still suffer from moderate photoluminescence quantum yields. Recent efforts have focused on tailoring their emission properties. Introducing zwitterionic ligands to cap the metallic kernel is an efficient approach to enhance their one-photon excitation fluorescence intensity.