A Novel Approach for Non-Invasive Lung Imaging and Targeting Lung Immune Cells

Abstract

Despite developments in pulmonary radiotherapy, radiation-induced lung toxicity remains a problem. More sensitive lung imaging able to increase the accuracy of diagnosis and radiotherapy may help reduce this problem. Super-paramagnetic iron oxide nanoparticles are used in imaging, but without further modification can cause unwanted toxicity and inflammation. Complex carbohydrate and polymer-based coatings have been used, but simpler compounds may provide additional benefits. Herein, we designed and generated super-paramagnetic iron oxide nanoparticles coated with the neutral natural dietary amino acid glycine (GSPIONs), to support non-invasive lung imaging and determined particle biodistribution, as well as understanding the impact of the interaction of these nanoparticles with lung immune cells. These GSPIONs were characterized to be crystalline, colloidally stable, with a size of 12 ± 5 nm and a hydrodynamic diameter of 84.19 ± 18 nm. Carbon, Hydrogen, Nitrogen (CHN) elemental analysis estimated approximately 20.2 × 103 glycine molecules present per nanoparticle. We demonstrated that it is possible to determine the biodistribution of the GSPIONs in the lung using three-dimensional (3D) ultra-short echo time magnetic resonance imaging. The GSPIONs were found to be taken up selectively by alveolar macrophages and neutrophils in the lung. In addition, the GSPIONs did not cause changes to airway resistance or induce inflammatory cytokines. Alveolar macrophages and neutrophils are critical regulators of pulmonary inflammatory diseases, including allergies, infections, asthma and chronic obstructive pulmonary disease (COPD). Therefore, pulmonary Magnetic Resonance (MR) imaging and preferential targeting of these lung resident cells by our nanoparticles offer precise imaging tools, which can be utilized to develop precision targeted radiotherapy as well as diagnostic tools for lung cancer, thereby having the potential to reduce the pulmonary complications of radiation.

Therapeutic Potential of Thymoquinone and Its Nanoformulations in Pulmonary Injury: A Comprehensive Review

“…TQ was found to be effective in downregulating or reducing inflammatory responses, such as those associated with IL-1, IL-6, IL-10, IL-18, TNF-α, and NF-κB. 117 …”

“…TQ was found to be effective in downregulating or reducing inflammatory responses, such as those associated with IL-1, IL-6, IL-10, IL-18, TNF-α, and NF-κB. 117 Several recent reports have indicated that TQ reduces the levels of 5-lipoxygenase, leukotriene B4, C4, and Th2 cytokines in bronchoalveolar lavage (BAL) fluid with significant increments of eosinophilia and goblet cells in lung tissue. 116 In addition, TQ was found to alleviate the mRNA expression of inducible nitric oxide synthase and transforming growth factor β1 (TGF-β1).…”

Advanced Biomimetic Nanomaterials for Non-invasive Disease Diagnosis

“…The GSPIONs have stable structures and are easy to synthesize with a particle size of 12.5 nm and a hydrodynamic diameter of 84.19 ± 18 nm. These GSPIONs may provide an accurate diagnostic tool for lung cancer (Chakraborty et al, 2020). Yoo et al (2017) developed an activatable MRI contrast agent based on PEG-coated superparamagnetic iron oxide nanoparticles complexed with poly(gallol).…”

“…+, applicable; −, no report. Cancer (Xu et al, 2018;Yarbakht et al, 2018;Hu et al, 2019;Nicolson et al, 2019;Chakraborty et al, 2020)…”

Nanoparticle-Based Radiosensitization

“…Radiolabeling of nanoparticles was reviewed by Prof. Jeon [12], who summarised nuclides useful for various imaging modalities and also offered therapeutic opportunities via their decay and emissions. Similar concepts were reported in work from Prof. Selomulya and Prof. Plebanski in Chakraborty et al [13], but within the context of magnetic resonance imaging. Magnetic properties of iron oxide nanoparticles were used for imaging selective uptake by alveolar macrophages and neutrophils in the lung with the aim of assisting diagnostics and radiotherapy planning, and reducing the pulmonary complications of radiation.…”