Ryan F. Landis

Gold Nanoparticles for Nucleic Acid Delivery

Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell.

Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms.

Bacterial biofilms are widely associated with persistent infections. High resistance to conventional antibiotics and prevalent virulence makes eliminating these bacterial communities challenging therapeutic targets. We describe here the fabrication of a nanoparticle-stabilized capsule with a multicomponent core for the treatment of biofilms. The peppermint oil and cinnamaldehyde combination that comprises the core of the capsules act as potent antimicrobial agents. An in situ reaction at the oil/water interface between the nanoparticles and cinnamaldehyde structurally augments the capsules to efficiently deliver the essential oil payloads, effectively eradicating biofilms of clinically isolated pathogenic bacteria strains. In contrast to their antimicrobial action, the capsules selectively promoted fibroblast proliferation in a mixed bacteria/mammalian cell system making them promising for wound healing applications.

Ultrastable and Biofunctionalizable Gold Nanoparticles

Gold nanoparticles provide an excellent platform for biological and material applications due to their unique physical and chemical properties. However, decreased colloidal stability and formation of irreversible aggregates while freeze-drying nanomaterials limit their use in real world applications. Here, we report a new generation of surface ligands based on a combination of short oligo (ethylene glycol) chains and zwitterions capable of providing nonfouling characteristics while maintaining colloidal stability and functionalization capabilities. Additionally, conjugation of these gold nanoparticles with avidin can help the development of a universal toolkit for further functionalization of nanomaterials.

Nanoparticle-Based Antimicrobials: Surface Functionality is Critical

Bacterial infections cause 300 million cases of severe illness each year worldwide. Rapidly accelerating drug resistance further exacerbates this threat to human health. While dispersed (planktonic) bacteria represent a therapeutic challenge, bacterial biofilms present major hurdles for both diagnosis and treatment. Nanoparticles have emerged recently as tools for fighting drug-resistant planktonic bacteria and biofilms. In this review, we present the use of nanoparticles as active antimicrobial agents and drug delivery vehicles for antibacterial therapeutics. We further focus on how surface functionality of nanomaterials can be used to target both planktonic bacteria and biofilms.

Fully Zwitterionic Nanoparticle Antimicrobial Agents through Tuning of Core Size and Ligand Structure

Zwitterionic nanoparticles are generally considered nontoxic and noninteracting. Here, we report effective and selective antimicrobial activity of zwitterionic gold nanoparticles (AuNP) through modulation NP size and surface charge orientation. Using a set of 2, 4, and 6 nm core AuNPs, increasing particle size increased antimicrobial efficiency through bacterial membrane disruption. Further improvement was observed through control of the ligand structure, generating antimicrobial particles with low hemolytic activity and demonstrating the importance of size and surface structure in dictating the bioactivity properties of nanomaterials.

Cross-Linked Polymer-Stabilized Nanocomposites for the Treatment of Bacterial Biofilms

Infections caused by bacterial biofilms are an emerging threat to human health. Conventional antibiotic therapies are ineffective against biofilms due to poor penetration of the extracellular polymeric substance secreted by colonized bacteria coupled with the rapidly growing number of antibiotic-resistant strains. Essential oils are promising natural antimicrobial agents; however, poor solubility in biological conditions limits their applications against bacteria in both dispersed (planktonic) and biofilm settings. We report here an oil-in-water cross-linked polymeric nanocomposite (∼250 nm) incorporating carvacrol oil that penetrates and eradicates multidrug-resistant (MDR) biofilms. The therapeutic potential of these materials against challenging wound biofilm infections was demonstrated through specific killing of bacteria in a mammalian cell-biofilm coculture wound model.

Continuous synthesis of high quality CdSe quantum dots in supercritical fluids

We demonstrate in here a powerful scalable technology to synthesize continuously high quality CdSe quantum dots (QDs) in supercritical hexane. Using a low cost, highly thermally stable Cd-precursor, cadmium deoxycholate, the continuous synthesis is performed in 400 μm ID stainless steel capillaries resulting in CdSe QDs having sharp full-width-at-half-maxima (23 nm) and high photoluminescence quantum yields (45–55%). Transmission electron microscopy images show narrow particles sizes distribution (σ ≤ 5%) with well-defined crystal lattices. Using two different synthesis temperatures (250 °C and 310 °C), it was possible to obtain zinc blende and wurtzite crystal structures of CdSe QDs, respectively. This synthetic approach allows achieving substantial production rates up to 200 mg of QDs per hour depending on the targeted size, and could be easily scaled to gram per hour.

Hybrid Organic–Inorganic Colloidal Composite ‘Sponges’ via Internal Crosslinking

An effective method for the generation of hybrid organic-inorganic nanocomposite microparticles featuring controlled size and high structural stability is presented. In this process, an oil-in-water Pickering emulsion is formed using hydrophilic amine-functionalized silica nanoparticles. Covalent modification using a hydrophobic maleic anhydride copolymer then alters nanoparticle wettability during crosslinking, causing a core-shell to nanocomposite structural reorganization of the assemblies. The resulting porous nanocomposites maintain discrete microparticle structures and retain payloads in their oil phase even when incubated in competitive solvents such as ethanol.

Enhanced Laser Desorption/Ionization Mass Spectrometric Detection of Gold Nanoparticles in Biological Samples Using the Synergy between Added Matrix and the Gold Core

Laser desorption/ionization mass spectrometry (LDI-MS) has been used to detect gold nanoparticles (AuNPs) in biological samples, such as cells and tissues, by ionizing their attached monolayer ligands. Many NP-attached ligands, however, are difficult to ionize by LDI, making it impossible to track these NPs in biological samples. In this work, we demonstrate that concentrations of matrix-assisted LDI (MALDI) matrices an order of magnitude below the values typically used in MALDI can facilitate the selective detection of AuNPs with these ligands, even in samples as complex as cell lysate. This enhanced sensitivity arises from a synergistic relationship between the gold core and the matrix that helps to selectively ionize ligands attached to the AuNPs.

Sensing by Smell: Nanoparticle–Enzyme Sensors for Rapid and Sensitive Detection of Bacteria with Olfactory Output

We present here a highly efficient sensor for bacteria that provides an olfactory output, allowing detection without the use of instrumentation and with a modality that does not require visual identification. The sensor platform uses nanoparticles to reversibly complex and inhibits lipase. These complexes are disrupted in the presence of bacteria, restoring enzyme activity and generating scent from odorless pro-fragrance substrate molecules. This system provides rapid (15 min) sensing and very high sensitivity (102 cfu/mL) detection of bacteria using the human sense of smell as an output.