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.
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.
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.
Quantum dots were used as fluorescent probes to investigate nanoparticle penetration into biofilms. The particle penetration behavior was found to be controlled by surface chemical properties.
Zwitterionic nanoparticles are generally considered non-toxic and non-interacting. 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 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.
The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semirigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of polymeric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial resistance toward these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant antibiotics where significant resistance occurred after only a few passages.
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, limits their use in real world applications. Here, we report a new generation of surface ligands based on a combination of short oligo (ethylene glycol) chain and zwitterions capable of providing non-fouling characteristics, while maintaining colloidal stability and functionalization capabilities. Additionally, conjugation of these gold nanoparticles with avidin can help developing a universal toolkit for further functionalization of nanomaterials.
Infections caused by multidrug-resistant (MDR) bacteria are a rapidly growing threat to human health, in many cases exacerbated by their presence in biofilms. We report here a biocompatible oil-in-water cross-linked polymeric nanocomposite that degrades in the presence of physiologically relevant biomolecules. These degradable nanocomposites demonstrated broad-spectrum penetration and elimination of MDR bacteria, eliminating biofilms with no toxicity to cocultured mammalian fibroblast cells. Notably, serial passaging revealed that bacteria were unable to develop resistance toward these nanocomposites, highlighting the therapeutic promise of this platform.
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