Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells

Sweeney, Sinbad; Leo, Bey Fen; Chen, Shu; Abraham-Thomas, Nisha; Thorley, Andrew J.; Gow, Andrew J.; Schwander, Stephan; Zhang, Junfeng Jim; Shaffer, Milo S. P.; Chung, Kian Fan; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

doi:10.1016/j.colsurfb.2016.04.040

Cited by 31 publications

(16 citation statements)

References 38 publications

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“…In support of this, evidence that AgNP induce inflammation is largely present in the literature. Sweeney et al (2016) showed that AgNP induced secretion of IL-6 and IL-8 in mouse neuronal cells human alveolar type-I-like epithelial cells. In the same manner, Murphy et al (2016) demonstrated increased gene expression of IL-1, IL-6 and TNF-α and increased secretion of pro-IL-1β upon exposure of THP-1 and primary human blood monocytes to AgNP.…”

Section: Discussionmentioning

confidence: 99%

“…Taken together, repeated human exposure to AgNP may result in chronic inflammation that may favour autoimmunity or cancer development and the wide application of AgNP increases risk of AgNP induced adverse effects. In this study, we encapsulated AgNP within a dipalmitoyl phosphatidylcholine (DPPC)-based liposome to suppress the nanoparticle-induced inflammation, based on previous studies that have shown that DPPC suppresses AgNP induced inflammation (Murphy et al, 2015;Sweeney et al, 2016). We then showed that the liposomal encapsulation of AgNP suppresses AgNP induced inflammation in both THP1 monocytes and THP1 cells differentiated into macrophages and the exposure to liposomal AgNP correlates with inhibition of STAT-3 expression.…”

Section: Introductionmentioning

confidence: 99%

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Surface modification of silver nanoparticle (AgNP) by liposomal encapsulation mitigates AgNP-induced inflammation

Yusuf

Casey

2019

Toxicology in Vitro

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Silver nanoparticles (AgNP) are widely used in a variety of consumable products as antibacterial to prevent or treat infection. Unfortunately, evidence exits that AgNP induces inflammation which can worsen with repeated human exposure. However, there is little or no research on how to mitigate these adverse effects due to AgNP induced-toxicity. Here, we investigated if surface modification of AgNP by liposomal encapsulation suppresses AgNP-mediated inflammatory responses in THP1 monocytes and THP1 differentiated macrophages (TDM). AgNP was encapsulated in a dipalmitoyl phosphatidyl choline-(DPPC)/cholesterol-based liposome by extrusion through a 100-nm polycarbonate membrane to form Lipo-AgNP. It was found as expected that AgNP induced significant release of IL-1β, IL-6, IL-8 and TNF-α in THP1 monocytes more than the basal level. Interestingly, release of these cytokines was suppressed by Lipo-AgNP. In TDMs, AgNP and Lipo-AgNP induced IL-8 release (p < .0001), but Lipo-AgNP maintained IL-8 release at levels significantly lower than that of AgNP (p < .01). However, both AgNP and Lipo-AgNP suppressed IL-1β and TNF-α release in LPS-stimulated THP1 monocytes and LPS-stimulated or unstimulated TDM respectively. We finally showed that Lipo-AgNP inhibits STAT-3 and this may be responsible for regulating the uncontrolled inflammation induced by AgNP likely mediated STAT-3 protein expression in LPS stimulated THP1 monocytes and TDMs, both LPS-stimulated and unstimulated. This data showed that Lipo-AgNP suppressed AgNP induced inflammation, making Lipo-AgNP particularly useful in treatment of bacteria induced inflammatory diseases and inflammatory cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Surface modification of silver nanoparticle (AgNP) by liposomal encapsulation mitigates AgNP-induced inflammation

Yusuf

Casey

2019

Toxicology in Vitro

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“…Studies on immortalization of primary alveolar epithelial cells are more limited. Kemp et al developed an immortalized human AEC1-like (transformed type-1; TT1) cell line by transduction with the catalytic subunit of telomerase (hTERT) and simian virus 40 large-tumour antigen (Kemp et al, 2008), and this line was used in studies on nanoparticles toxicity (Sweeney et al, 2016).…”

Section: Mucociliairy Clearancementioning

confidence: 99%

Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

Hiemstra

Grootaers

Does

et al. 2018

Toxicology in Vitro

147

116

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A B S T R A C TThe epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the biological effects of inhaled toxicants. However, the validity of the current in vitro models and their acceptance by regulatory authorities as an alternative to animal models is a reason for concern, and requires a critical review. In this review, focused on human lung epithelial cell cultures as a model for inhalation toxicology, we discuss the choice of cells for these models, the cell culture system used, the method of exposure as well as the various read-outs to assess the cellular response. We argue that rapid developments in the 3D culture of primary epithelial cells, the use of induced pluripotent stem cells for generation of lung epithelial cells and the development of organ-on-a-chip technology are among the important developments that will allow significant advances in this field. Furthermore, we discuss the various routes of application of inhaled toxicants by air-liquid interface models as well as the vast array of read-outs that may provide essential information. We conclude that close collaboration between researchers from various disciplines is essential for development of valid methods that are suitable for replacement of animal studies for inhalation toxicology.

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“…PS was thought to be biocompatible, biodegradable and non‐immunogenic. It could mitigate silver nanoparticle toxicity in human alveolar type I‐like epithelial cells . PHT was the synthetic analogues of PS.…”

Section: Discussionmentioning

confidence: 99%

“…It could mitigate silver nanoparticle toxicity in human alveolar type I-like epithelial cells. [36] PHT was the synthetic analogues of PS. Insulin exhibits growth factor activity by weakly binding to the insulin-like growth factor receptor with <1/100th the potency of insulin-like growth factor 1(IGF1).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of inhaled recombinant human insulin dry powders: pharmacokinetics, pharmacodynamics and 14-day inhalation

Zhang

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives The present study was designed to assess the pharmacokinetic and pharmacodynamic performance of inhaled recombinant human insulin (rh‐insulin) dry powders together with their safety profiles after 14‐day inhalation. Methods In the pharmacokinetic and pharmacodynamic study, pulmonary surfactant (PS)‐loaded and phospholipid hexadecanol tyloxapol (PHT)‐loaded rh‐insulin dry powders were intratracheally administered to male rats at the dose of 20 U/kg. Novolin R was used as control. Serum glucose and rh‐insulin concentrations were determined by glucose oxidase method and human rh‐insulin CLIA kit, respectively. For the safety study, rats were exposed to rh‐insulin dry powders or air for 14‐day by nose‐only inhalation chambers. Bronchoalveolar lavage and histopathology examinations were performed after inhalation. Key findings There were no significant differences in the major pharmacokinetic and pharmacodynamic parameters between PS‐loaded and PHT‐loaded rh‐insulin dry powders. The relative bioavailabilities and pharmacodynamic availabilities were 39.9%, 25.6% for PS‐loaded dry powders and 30.1%, 23% for PHT‐loaded dry powders, respectively. Total protein was the only injury marker that was significantly altered. Histopathology examinations showed the ranking of irritations (from slight to severe) were PHT‐loaded rh‐insulin, negative air control and PS‐loaded rh‐insulin. Conclusions Both PS‐ and PHT‐loaded rh‐insulin dry powders were able to deliver rh‐insulin systemically with appropriate pharmacokinetic, pharmacodynamic and safety profiles.

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Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells

Cited by 31 publications

References 38 publications

Surface modification of silver nanoparticle (AgNP) by liposomal encapsulation mitigates AgNP-induced inflammation

Surface modification of silver nanoparticle (AgNP) by liposomal encapsulation mitigates AgNP-induced inflammation

Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

Evaluation of inhaled recombinant human insulin dry powders: pharmacokinetics, pharmacodynamics and 14-day inhalation

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