Inflammation-modulating nanoparticles for pneumonia therapy.

Pneumonia is a common but serious infectious disease, and is the sixth leading cause for death. The foreign pathogens such as viruses, fungi, and bacteria establish an inflammation response after interaction with lung, leading to the filling of bronchioles and alveoli with fluids. Although the pharmacotherapies have shown their great effectiveness to combat pathogens, advanced methods are under developing to treat complicated cases such as virus-infection and lung inflammation or acute lung injury (ALI). The inflammation modulation nanoparticles (NPs) can effectively suppress immune cells and inhibit inflammatory molecules in the lung site, and thereby alleviate pneumonia and ALI. In this review, the pathological inflammatory microenvironments in pneumonia, which are instructive for the design of biomaterials therapy, are summarized. The focus is then paid to the inflammation-modulating NPs that modulate the inflammatory cells, cytokines and chemokines, and microenvironments of pneumonia for better therapeutic effects. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.

ROS-responsive polymer nanoparticles with enhanced loading of dexamethasone effectively modulate the lung injury microenvironment.

The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients as currently seen in coronavirus disease 2019 (COVID-19). There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to lung to reduce the burden of high doses of medications and attenuate inflammatory cells and pathways. Herein, we prepared dexamethasone-loaded ROS-responsive polymer nanoparticles (PFTU@DEX NPs) by a modified emulsion approach, which achieved high loading content of DEX (11.61 %). DEX was released faster from the PFTU@DEX NPs in a ROS environment, which could scavenge excessive ROS efficiently both in vitro and in vivo. The PFTU NPs and PFTU@DEX NPs showed no hemolysis and cytotoxicity. Free DEX, PFTU NPs and PFTU@DEX NPs shifted M1 macrophages to M2 macrophages in RAW264.7 cells, and showed anti-inflammatory modulation to A549 cells in vitro. The PFTU@DEX NPs treatment significantly reduced the increased total protein concentration in BALF of ALI mice. The delivery of PFTU@DEX NPs decreased the proportion of neutrophils significantly, mitigated the cell apoptosis remarkably compared to the other groups, reduced M1 macrophages and increased M2 macrophages in vivo. Moreover, the PFTU@DEX NPs had the strongest ability to suppress the expression of NLRP3, Caspase1, and IL-1ß. Therefore, the PFTU@DEX NPs could efficiently suppress inflammatory cells, ROS signaling pathways, and cell apoptosis to ameliorate LPS-induced ALI. STATEMENT OF SIGNIFICANCE: The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients. There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to modulate the inflammatory disorder and suppress the expression of ROS and inflammatory cytokines. The inhaled PFTU@DEX NPs prepared through a modified nanoemulsification method suppressed the activation of NLRP3, induced the polarization of macrophage phenotype from M1 to M2, and thereby reduced the neutrophil infiltration, inhibited the release of proteins and inflammatory mediators, and thus decreased the acute lung injury in vivo.

Dexamethasone-loaded ROS-responsive poly(thioketal) nanoparticles suppress inflammation and oxidative stress of acute lung injury

Acute lung injury (ALI) is associated with excessive inflammatory response, leading to acute respiratory distress syndrome (ARDS) without timely treatment. A fewer effective drugs are available currently to treat the ALI/ARDS. Herein, a therapeutic nanoplatform with reactive oxygen species (ROS)-responsiveness was developed for the regulation of inflammation. Dexamethasone acetate (Dex) was encapsulated into poly(thioketal) polymers to form polymeric nanoparticles (NPs) (PTKNPs@Dex). The NPs were composed of poly(1,4-phenyleneacetonedimethylene thioketal) (PPADT) and polythioketal urethane (PTKU), in which the thioketal bonds could be cleaved by the high level of ROS at the ALI site. The PTKNPs@Dex could accumulate in the pulmonary inflammatory sites and release the encapsulated payloads rapidly, leading to the decreased ROS level, less generation of pro-inflammatory cytokines, and reduced lung injury and mortality of mice. RNA sequencing (RNA-seq) analysis showed that the therapeutic efficacy of the NPs was associated with the modulation of many immune and inflammation-linked pathways. These findings provide a newly developed nanoplatform for the efficient treatment of ALI/ARDS. Graphical A therapeutic nanoplatform composed of low Mw of poly(1,4-phenyleneacetonedimethylene thioketal) and high Mw of polythioketal urethane was developed with the feature of ROS scavenging and anti-inflammation. The dexamethasone acetate-loaded NPs significantly decreased lung inflammation, and reduced lung injury and mortality in vivo.Image 1 Highlights • A therapeutic nanoplatform with ROS-responsiveness was developed for the regulation of inflammation.• NPs composed of low Mw of PPADT and high Mw of PTKU were loaded with dexamethasone to obtain a self-adaptive system.• The Dex-loaded NPs significantly decreased lung inflammation, and reduced lung injury and mortality in vivo.

Antiviral Activity of Nanomaterials against Coronaviruses.

One of the challenges facing by world nowadays is the generation of new pathogens that cause public health issues. Coronavirus (CoV) is one of the severe pathogens that possess the RNA (ribonucleic acid) envelop, and extensively infect humans, birds, and other mammals. The novel strain "SARS-CoV-2" (severe acute respiratory syndrome coronavirus-2) causes deadly infection all over the world and presents a pandemic situation nowadays. The SARS-CoV-2 has 40 different strains that create a worrying situation for health authorities. The virus develops serious pneumonia in infected persons and causes severe damage to the lungs. There is no vaccine available for this virus up to present. To cure this type of infections by making vaccines and antiviral drugs is still a major challenge for researchers. Nanotechnology covering a multidisciplinary field may find the solution to this lethal infection. The interaction of nanomaterials and microorganisms is considered as a potential treatment method because the nanomaterials owe unique physicochemical properties. The aim of this review is to present an overview of previous and recent studies of nanomaterials against coronaviruses and to provide possible new strategies for upcoming research using the nanotechnology platform.