Nucleic acid peptide nanogels for the treatment of bacterial keratitis

Obuobi, Sybil; Mayandi, Venkatesh; Nor, Nurul Azlyn Mohd; Lee, Benedict Jiasheng; Lakshminarayanan, Rajamani; Ee, Pui Lai Rachel

doi:10.1039/d0nr03095c

Cited by 26 publications

(23 citation statements)

References 59 publications

(61 reference statements)

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“…Two studies from Obuobi et al utilized the same DNA-based nanogel formulation described above for VAN delivery, however, substituted the positively charged glycopeptide antibiotic with a broad-spectrum AMP, L12. [112,113] This AMP was previously shown to be effective against a large number of bacteria, Figure 6. Transport of peptide-and enzyme-based bactericidal substances.…”

Section: Antimicrobial Peptides and Enzymesmentioning

confidence: 99%

“…Two studies from Obuobi et al utilized the same DNA‐based nanogel formulation described above for VAN delivery, however, substituted the positively charged glycopeptide antibiotic with a broad‐spectrum AMP, L12. [ 112,113 ] This AMP was previously shown to be effective against a large number of bacteria, including both drug‐susceptible and multidrug‐resistant species. [ 114 ] A similar assembly approach was used as described earlier; however, subtle alterations led to either a condensed DNA hydrogel suitable for application as a wound dressing [ 112 ] or discrete DNA nanogels that could be locally applied to eye infections.…”

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

“…[ 114 ] A similar assembly approach was used as described earlier; however, subtle alterations led to either a condensed DNA hydrogel suitable for application as a wound dressing [ 112 ] or discrete DNA nanogels that could be locally applied to eye infections. [ 113 ] The hydrogel formulation was able to effectively kill MRSA, E. coli and P. aeruginosa in in vitro tests, and were particularly effective against MRSA, likely due to the species’ natural secretion of high amounts of nucleases leading to quicker release of the AMP (see Figure 6b). The antibacterial properties of the hydrogel as a potential wound dressing were tested in an ex vivo explant model, consisting of sections of porcine skin that was infected with S. aureus .…”

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

“…Showing the versatility of this method, discrete, compact nanogels of 100–500 nm were also loaded with AMP‐L12 and used as a treatment of bacterial keratitis or simply, bacterial‐induced inflammation of the eye, in mice. [ 113 ] Again, the same panel of three bacteria was used to confirm the formulations ability to release the AMP into solution and effectively inhibit their growth, and additional in vivo validation was conducted with S. aureus . An artificial wound was generated in the eyes of mice by removing part of the cornea, they were treated with the bacteria, and the DNA nanogel formulations were applied 6 h postinfection.…”

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

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DNA Nanostructures in the Fight Against Infectious Diseases

Smith

Keller

2021

Advanced NanoBiomed Research

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The ongoing COVID-19 pandemic has once more led to the realization that humanity is dangerously ill prepared for fighting the threats associated with epidemic outbreaks of infectious diseases. COVID-19 is only the latest in a long list of viral diseases, including SARS, [1] MERS, [2] Zika, [3] Ebola, [4] and Nipah, [5] that emerged as severe threats to public health in the past two decades and that continue to threaten human lives. However, also diseases that have plagued humanity for centuries still present a severe burden. For instance, the 20th century has seen three influenza pandemics with death tolls in the millions [6] and the seasonal flu still kills on average an estimated 389 000 people each year. [7] Furthermore, due to the global rise of antibiotic resistance in the past few decades, bacterial infections have once again become a severe threat to human health. [8] In 2015, about 670 000 patients in the EU alone suffered from infections with antibiotic-resistant strains of eight bacterial pathogens, resulting in 33 000 deaths. [9] The situation in the US is similar, with an estimated 23 000 deaths each year as a direct result of more than 2 million multidrug-resistant infections. [10] In low-and middle-income countries with limited ability to pay for second-line drugs, antibiotic resistance results in even higher mortality rates. In 2010, about 38 000 deaths in Thailand alone were attributed to infections with only five antibiotic-resistant bacteria. [11] In India, it is estimated that about 60 000 neonatal deaths each year result from antibiotic-resistant bacterial infections. [8] More recently, the worldwide emergence of antifungal resistance has raised grave concerns as well, [12] as invasive fungal infections are responsible for at least 2 million life-threatening

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Section: Antimicrobial Peptides and Enzymesmentioning

confidence: 99%

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

See 2 more Smart Citations

DNA Nanostructures in the Fight Against Infectious Diseases

Smith

Keller

2021

Advanced NanoBiomed Research

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“…It was successful that antimicrobial peptides were confined within the DNA nanogel via the binding affinity of L12 to the polyanionic core (Figure 19). [196] Figure 19. Utility of peptide-loaded DNA nanogels for treatment of topical bacterial keratitis.…”

Section: Integrated Nucleic Acids-materials Hybrid System For Antimic...mentioning

confidence: 99%

Materialistic Interfaces with Nucleic Acids: Principles and Their Impact

Zhang

et al. 2022

Adv Funct Materials

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Mendelian genetics spark the century‐old revolution in genetic engineering. DNA structural engineering may well spark a similar revolution in chemistry. The first few man‐made DNA structures are purely DNA but increased interest in hybrid DNA with other molecules is regaining popularity. Nucleic acids can interact with non‐nucleic acid‐based materials, showing their materialistic flexibility and potential and the prospect of forming new future materials. This review provides a deep materialistic background based on the interaction of nucleic acids with these non‐nucleic acid‐based materials covering comprehensive topics. The non‐nucleic acid materials are broadly divided into biological materials, for example, small‐biomolecules, peptides, proteins, and lipids, and non‐biological materials consisting of metal ions, chemical molecules, low‐dimensional nanomaterials, and micro‐scale polymers. Of significance, combining the unique properties of nucleic acids with these non‐genetic materials can bring about surprising synergistic characteristics and drive attractive applications in bio‐imaging, chem/bio‐sensing, disease therapies, antimicrobial works, and even information storage.

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In Vivo Interactions of Nucleic Acid Nanostructures With Cells

Xiao,

Liang,

Shyngys

et al. 2024

Advanced Materials

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Nucleic acid nanostructures, derived from the assembly of nucleic acid building blocks (e.g., plasmids and oligonucleotides), are important intracellular carriers of therapeutic cargoes widely utilized in preclinical nanomedicine applications, yet their clinical translation remains scarce. In the era of “translational nucleic acid nanotechnology”, a deeper mechanistic understanding of the interactions of nucleic acid nanostructures with cells in vivo will guide the development of more efficacious nanomedicines. This review showcases the recent progress in dissecting the in vivo interactions of four key types of nucleic acid nanostructures (i.e., tile‐based, origami, spherical nucleic acid, and nucleic acid nanogel) with cells in rodents over the past five years. Emphasis lies on the cellular‐level distribution of nucleic acid nanostructures in various organs and tissues and the cellular responses induced by their cellular entry. Next, in the spirit of preclinical translation, this review features the latest interactions of nucleic acid nanostructures with cells in large animals and humans. Finally, the review offers directions for studying the interactions of nucleic acid nanostructures with cells from both materials and biology perspectives and concludes with some regulatory updates.

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Nucleic acid peptide nanogels for the treatment of bacterial keratitis

Abstract: DNA nanogels were developed with rapid in situ loading of L12 peptides during thermal hybridization. This facile strategy retained peptide efficacy to achieve fast resolution of bacterial keratitis.

Cited by 26 publications

References 59 publications

DNA Nanostructures in the Fight Against Infectious Diseases

DNA Nanostructures in the Fight Against Infectious Diseases

Materialistic Interfaces with Nucleic Acids: Principles and Their Impact

In Vivo Interactions of Nucleic Acid Nanostructures With Cells

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