Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

The therapeutic approach for the treatment of HIV infection is based on the highly active antiretroviral therapy (HAART), a cocktail of antiretroviral drugs. Notwithstanding HAART has shown different drawbacks like toxic side effects and the emergence of viral multidrug resistance. Nanotechnology offers new tools to improve HIV drug treatment and prevention. In this scenario, gold nanoparticles are an interesting chemical tool to design and prepare smart and efficient drug-delivery systems. Here we describe the preparation and antiviral activity of carbohydrate-coated gold nanoparticles loaded with anti-HIV prodrug candidates. The nucleoside reverse transcriptase inhibitors abacavir and lamivudine have been converted to the corresponding thiol-ending ester derivatives and then conjugated to ~3 nm glucose-coated gold nanoparticles by means of “thiol-for-thiol” ligand place exchange reactions. The drugs-containing glyconanoparticles were characterized and the pH-mediated release of the drug from the nanoparticle has been determined. The antiviral activity was tested by evaluating the replication of NL4-3 HIV in TZM-bl infected cells. The proof-of-principle presented in this work aims to introduce gold glyconanoparticles as a new multifunctional drug-delivery system in the therapy against HIV

Galactose‐Functionalized Gold Nanoparticles Targeting Membrane Transporters for the Glutathione Delivery to Brain Cancer Cells

Glutathione (GSH), a tripeptide essential for maintaining redox balance in the human body, plays a critical role in protecting cells from oxidative stress. A deficiency in GSH is linked to increased oxidative damage and the progression of various disorders, including cancer and neurological diseases. Herein, gold nanoparticles (Au NPs) coated with GSH and further functionalized with galactose moieties are developed to selectively target glucose transporters (GLUT), which is overexpressed on the surface of the blood-brain barrier (BBB) and could be exploited for the selective recognition and internalization of the Au@GSH-Gal NPs, that could then exert an antioxidant effect. As a proof of concept, brain cancer cells are treated with Au@GSH-Gal NPs, evidencing their increased internalization and a significant reduction of H2O2-induced oxidative stress

Development of a novel, compact, and transportable multispectral imaging device for wound healing monitoring

Multispectral imaging (MSI) devices are optical diagnostic tools that can be used for the non-invasive monitoring and characterization of various kinds of pathologies, including skin conditions such as wounds and ulcers, due to the capability of such technology to track alterations of structural and physiological parameters (e.g., oxygenation and haemodynamics) from changes in the optical properties of the investigated tissue across a large number of spectral bands. In this work, a novel, compact and transportable MSI device based on spectral scanning and diffuse reflectance imaging is going to be presented. The apparatus is composed of light emitting diodes (LEDs) as light sources and a CMOS camera, making it a very compact, manageable, user-friendly, and cost-effective system. The wavelengths of the LED sources, that are located in the visible-NIR portion of the spectrum, have been specifically selected to target and monitor alterations of oxygenation and haemodynamics that can provide biomarkers of monitoring wound healing in chronic ulcers. The calibration of the MSI system is going to be illustrated, discussing the calibration procedure and results obtained with (1) Monte Carlo-based, digital phantoms and (2) liquid optical phantoms. Both types of phantoms mimic the properties of biological tissues and allow to introduce variations in a controlled manner. The proposed MSI system is also going to be tested on patients affected by chronic skin ulcers in order to assess its efficacy and accuracy

Neutralization of ionic interactions by dextran-based single-chain nanoparticles improves tobramycin diffusion into a mature biofilm

The extracellular matrix protects biofilm cells by reducing diffusion of antimicrobials. Tobramycin is an antibiotic used extensively to treat P. aeruginosa biofilms, but it is sequestered in the biofilm periphery by the extracellular negative charge matrix and loses its efficacy significantly. Dispersal of the biofilm extracellular matrix with enzymes such as DNase I is another promising therapy that enhances antibiotic diffusion into the biofilm. Here, we combine the charge neutralization of tobramycin provided by dextran-based single-chain polymer nanoparticles (SCPNs) together with DNase I to break the biofilm matrix. Our study demonstrates that the SCPNs improve the activity of tobramycin and DNase I by neutralizing the ionic interactions that keep this antibiotic in the biofilm periphery. Moreover, the detailed effects and interactions of nanoformulations with extracellular matrix components were revealed through time-lapse imaging of the P. aeruginosa biofilms by laser scanning confocal microscopy with specific labeling of the different biofilm components

Preparation and immunogenicity of gold glyco-nanoparticles as antipneumococcal vaccine model

Nanotechnology-based fully synthetic carbohydrate vaccines are promising alternatives to classic polysaccharide/protein conjugate vaccines. We have prepared gold glyco-nanoparticles (GNP) bearing two synthetic carbohydrate antigens related to serotypes 19F and 14 of Streptococcus pneumoniae and evaluated their immunogenicity in vivo. Results: A tetrasaccharide fragment of serotype 14 (Tetra-14), a trisaccharide fragment of serotype 19F (Tri-19F), a T-helper peptide and d -glucose were loaded onto GNP in different ratios. Mice immunization showed that the concomitant presence of Tri-19F and Tetra-14 on the same nanoparticle critically enhanced the titers of specific IgG antibodies toward type 14 polysaccharide compared with GNP exclusively displaying Tetra-14, while no IgG antibodies against type 19F polysaccharide were elicited. Conclusion: This work is a step forward toward synthetic nanosystems combining carbohydrate antigens and immunogenic peptides as potential carbohydrate-based vaccines