Probing the size limit for nanomedicine penetration into Burkholderia multivorans and Pseudomonas aeruginosa biofilms

Forier, Katrien; Messiaen, Anne-Sophie; Raemdonck, Koen; Nelis, Hans; Smedt, Stefaan C. De; Demeester, Jo; Coenye, Tom; Braeckmans, Kevin

doi:10.1016/j.jconrel.2014.07.061

Cited by 87 publications

(78 citation statements)

References 52 publications

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“…71,74,75 The diffusion of polystyrene (PS) nanoparticles (NP) and antibioticloaded liposomes is greatly hindered within the extracellular matrix of biofilms produced by bacteria commonly found in the lungs of CF patients, including Pseudomonas aeruginosa and Burkhedia cepacia complex. [76][77][78] As such, bacterial biofilms may represent an additional extracellular barrier component unique to CF airway mucus that must be overcome by inhaled gene vectors.…”

Section: Mucus In Individuals With Lung Diseasementioning

confidence: 99%

The Mucus Barrier to Inhaled Gene Therapy

et al. 2016

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Recent evidence suggests that the airway mucus gel layer may be impermeable to the viral and synthetic gene vectors used in past inhaled gene therapy clinical trials for diseases like cystic fibrosis. These findings support the logic that inhaled gene vectors that are incapable of penetrating the mucus barrier are unlikely to provide meaningful benefit to patients. In this review, we discuss the biochemical and biophysical features of mucus that contribute its barrier function, and how these barrier properties may be reinforced in patients with lung disease. We next review biophysical techniques used to assess the potential ability of gene vectors to penetrate airway mucus. Finally, we provide new data suggesting that fresh human airway mucus should be used to test the penetration rates of gene vectors. The physiological barrier properties of spontaneously expectorated CF sputum remained intact up to 24 hours after collection when refrigerated at 4 °C. Conversely, the barrier properties were significantly altered after freezing and thawing of sputum samples. Gene vectors capable of overcoming the airway mucus barrier hold promise as a means to provide the widespread gene transfer throughout the airway epithelium required to achieve meaningful patient outcomes in inhaled gene therapy clinical trials.

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Section: Mucus In Individuals With Lung Diseasementioning

confidence: 99%

The Mucus Barrier to Inhaled Gene Therapy

et al. 2016

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“…Bcc infection is usually planktonic and invasive, and the bacteria survive intracellularly in pulmonary macrophages and respiratory epithelial cells (14,15). Although biofilms are not typically observed, Bcc bacteria have been shown to form biofilms in vitro and to form mixed biofilms when cultured with P. aeruginosa (16)(17)(18). In addition, Bcc biofilms are more resistant to antibiotic cocktails than P. aeruginosa biofilms (19).…”

Section: T He Burkholderia Cepacia Complex (Bcc) Is Comprised Of 18mentioning

confidence: 99%

Short Palate, Lung, and Nasal Epithelial Clone 1 Has Antimicrobial and Antibiofilm Activities against the Burkholderia cepacia Complex

Ahmad

Tyrrell

Walton

et al. 2016

Antimicrob Agents Chemother

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The opportunistic bacteria of the Burkholderia cepacia complex (Bcc) are extremely pathogenic to cystic fibrosis (CF) patients, and acquisition of Bcc bacteria is associated with a significant increase in mortality. Treatment of Bcc infections is difficult because the bacteria are multidrug resistant and able to survive in biofilms. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) is an innate defense protein that is secreted by the upper airways and pharynx. While SPLUNC1 is known to have antimicrobial functions, its effects on Bcc strains are unclear. We therefore tested the hypothesis that SPLUNC1 is able to impair Bcc growth and biofilm formation. We found that SPLUNC1 exerted bacteriostatic effects against several Bcc clinical isolates, including B. cenocepacia strain J2315 (50% inhibitory concentration [IC 50 ] ‫؍‬ 0.28 M), and reduced biofilm formation and attachment (IC 50 ‫؍‬ 0.11 M). We then determined which domains of SPLUNC1 are responsible for its antimicrobial activity. Deletions of SPLUNC1's N terminus and ␣6 helix did not affect its function. However, deletion of the ␣4 helix attenuated antimicrobial activity, while the corresponding ␣4 peptide displayed antimicrobial activity. Chronic neutrophilia is a hallmark of CF lung disease, and neutrophil elastase (NE) cleaves SPLUNC1. However, we found that the ability of SPLUNC1 to disrupt biofilm formation was significantly potentiated by NE pretreatment. While the impact of CF on SPLUNC1-Bcc interactions is not currently known, our data suggest that understanding this interaction may have important implications for CF lung disease.

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“…The large scales of pMOFs are not conducive to the diffusion of ROS, resulting in modest photodynamic efficacy. Smaller nanoparticles have been reported to have better biofilm penetration . Recently, several targeted drug candidates were designed for antibacterial and cancer therapy to improve therapeutic efficiency .…”

Section: Introductionmentioning

confidence: 99%

Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

Deng

Sun

Zhang

et al. 2019

Adv Funct Materials

200

117

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Recently, antimicrobial photodynamic therapy (aPDT) has been considered as an attractive treatment option for biofilms ablation. However, even very efficient photosensitizers (PSs) still need high light doses and PS concentrations to eliminate biofilms due to the limited penetration and diffusion of PSs in biofilms. Moreover, the hypoxic microenvironment and rapid depletion of oxygen during PDT severely limit their therapeutic effects. Herein, for the first time, a porphyrin-based metal organic framework (pMOF) dots-based nanoplatform with effective biofilm penetration, self-oxygen generation, and enhanced photodynamic efficiency is synthesized for bacterial biofilms eradication. The function-adaptive nanoplatform is composed of pMOF dots encapsulated by human serum albumin-coated manganese dioxide (MnO 2 ). The pH/H 2 O 2responsive decomposition of MnO 2 in biofilms triggers the release of ultrasmall and positively charged pMOF dots and simultaneously generates O 2 insitu to alleviate hypoxia for biofilms. The released pMOF dots with high reactive oxygen species yield can effectively penetrate into biofilms, strongly bind with bacterial cell surface, and ablate bacterial biofilms. Importantly, such a nanoplatform can realize great therapeutic outcomes for treatment of Staphylococcus aureus-infected subcutaneous abscesses in vivo without damage to healthy tissues, which offers a promising strategy for efficient biofilms eradication.

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Probing the size limit for nanomedicine penetration into Burkholderia multivorans and Pseudomonas aeruginosa biofilms

Cited by 87 publications

References 52 publications

The Mucus Barrier to Inhaled Gene Therapy

The Mucus Barrier to Inhaled Gene Therapy

Short Palate, Lung, and Nasal Epithelial Clone 1 Has Antimicrobial and Antibiofilm Activities against the Burkholderia cepacia Complex

Porphyrin MOF Dots–Based, Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

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