Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

Chen, Xueyuan; Wang, Shanmei; Li, Nan; Hu, Yang; Zhang, Yuan; Xu, Jin‐Fu; Li, Xia; Ren, Jie; Su, Bo; Yuan, Weizhong; Teng, Xinying; Zhang, Rong-xuan; Jiang, Dianhua; Mulet, Xavier; Li, Huiping

doi:10.1371/journal.pone.0058275

Cited by 24 publications

(29 citation statements)

References 37 publications

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“…By parameters of tissue uptake and specificity vs the untargeted counterpart, the pulmonary accumulation of PACkET exceeds the best reported in the literature [11,45,46]. In theory, the hydrophilic biotinylated polyethylene oxide moiety of Pluronic is likely to be oriented away from the particle to aqueous medium, thereby enhancing steric freedom of Abs attached to distal PEO ends and facilitating targeting [47].…”

Section: Discussionmentioning

confidence: 99%

Endothelial targeting of nanocarriers loaded with antioxidant enzymes for protection against vascular oxidative stress and inflammation

et al. 2014

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Endothelial-targeted delivery of antioxidant enzymes, catalase and superoxide dismutase (SOD), is promising strategy for protecting organs and tissues from inflammation and oxidative stress. Here we describe Protective Antioxidant Carriers for Endothelial Targeting (PACkET), the first carriers capable of targeted endothelial delivery of both catalase and SOD. PACkET formed through controlled precipitation loaded ~30% enzyme and protected it from proteolytic degradation, whereas attachment of PECAM monoclonal antibodies to surface of the enzyme-loaded carriers, achieved without adversely affecting their stability and functionality, provided targeting. Isotope tracing and microscopy showed that PACkET exhibited specific endothelial binding and internalization in vitro. Endothelial targeting of PACkET was validated in vivo by specific (vs IgG-control) accumulation in the pulmonary vasculature after intravenous injection achieving 33% of injected dose at 30 min. Catalase loaded PACkET protects endothelial cells from killing by H2O2 and alleviated the pulmonary edema and leukocyte infiltration in mouse model of endotoxin-induced lung injury, whereas SOD-loaded PACkET mitigated cytokine-induced endothelial pro-inflammatory activation and endotoxin-induced lung inflammation. These studies indicate that PACkET offers a modular approach for vascular targeting of therapeutic enzymes.

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Section: Discussionmentioning

confidence: 99%

Endothelial targeting of nanocarriers loaded with antioxidant enzymes for protection against vascular oxidative stress and inflammation

et al. 2014

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“…Specifically, the resolution in ALI is characterized by the removal of neutrophils in the lung and the restoration of epithelial barrier function [38, 43]. Animal models have not been developed that fully to resemble human ALI but are quite useful for the better understanding of airway inflammation and the development of ALI [18, 44]. ALI experimental models in mouse, rat, rabbit, and guinea pigs are reported in the literature using different triggers, such as lipopolysaccharide (LPS), live bacteria, acid aspiration, and others.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, no therapeutic agents have demonstrated a clear benefit in ALI treatment [41], and corticosteroids have been used for treatment of ALI for many years [18, 53]. Besides, the disappointing results of a series of clinical trials treatment of ALI or patients at risk for ARDS using corticosteroids as well as the increase of the risk of infection and other adverse effects, the administration of corticosteroids might improve the injured tissue due to their anti-inflammatory effect [54].…”

Section: Introductionmentioning

confidence: 99%

Potential Effects of Medicinal Plants and Secondary Metabolites on Acute Lung Injury

Favarin

Oliveira

et al. 2013

BioMed Research International

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Acute lung injury (ALI) is a life-threatening syndrome that causes high morbidity and mortality worldwide. ALI is characterized by increased permeability of the alveolar-capillary membrane, edema, uncontrolled neutrophils migration to the lung, and diffuse alveolar damage, leading to acute hypoxemic respiratory failure. Although corticosteroids remain the mainstay of ALI treatment, they cause significant side effects. Agents of natural origin, such as medicinal plants and their secondary metabolites, mainly those with very few side effects, could be excellent alternatives for ALI treatment. Several studies, including our own, have demonstrated that plant extracts and/or secondary metabolites isolated from them reduce most ALI phenotypes in experimental animal models, including neutrophil recruitment to the lung, the production of pro-inflammatory cytokines and chemokines, edema, and vascular permeability. In this review, we summarized these studies and described the anti-inflammatory activity of various plant extracts, such as Ginkgo biloba and Punica granatum, and such secondary metabolites as epigallocatechin-3-gallate and ellagic acid. In addition, we highlight the medical potential of these extracts and plant-derived compounds for treating of ALI.

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“…To confirm the specific binding of Nb17 to rSPA, an irrelevant nanobody that did not recognize rSPA was generated and used as a negative control. As Figure 6A shows, the frequency change of Nb17 (∆f 17 ) was significantly higher than that of the control nanobody (∆f CTR ) by the passage of time, indicating the high binding ability between Nb17 and rSPA. These results suggest that our Nb17 possesses high specificity for rSPA.…”

Section: Production and Binding Specificity Of Anti-rspa Nanobodiesmentioning

confidence: 95%

“…We have successfully developed dexamethasone liposomes with active lung-targeting distribution by linking anti-SPA polyclonal antibodies (SPA-poly-ant) with a dexamethasone (DXM) nanoliposome (NLP) surface (SPA-DXM-NLP). 17 The concentration of the SPA-DXM-NLP complex in the lung is approximately fivefold greater than the free DXM control initially and reached 40-fold greater at 12 hours postinjection. Also, administration of SPA-DXM-NLP significantly attenuates lung injury in animal models.…”

Section: Introductionmentioning

confidence: 92%

A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

Wang¹,

He²,

Li³

et al. 2015

IJN

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Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery.

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Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

Cited by 24 publications

References 37 publications

Endothelial targeting of nanocarriers loaded with antioxidant enzymes for protection against vascular oxidative stress and inflammation

Endothelial targeting of nanocarriers loaded with antioxidant enzymes for protection against vascular oxidative stress and inflammation

Potential Effects of Medicinal Plants and Secondary Metabolites on Acute Lung Injury

A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting

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