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.
Highlights
Pulmonary radiotherapy is one of the standard treatments for non-small cell lung cancer [1]
We measured the hydrodynamic size of the GSPIONs using Dynamic Light Scatering (DLS) over eight replicates
The GSPIONs had an excellent poly-dispersity index (PDI) of 0.259, which signified a high amount of stability in suspension without clustering (Figure 1B)
Summary
Pulmonary radiotherapy is one of the standard treatments for non-small cell lung cancer [1]. One of the reasons for gratuitous complications with the use of pulmonary radiotherapy is the lack of high-precision radiation techniques as well as off-target effects [2]. Targeting nanoparticles for uptake by alveolar macrophages has recently been shown to be a useful intervention to treat lung cancer [21], and given their central role in the control of many diseases of the lung, it is likely to be useful across multiple diseases. Since uptake by alveolar macrophages of pro-inflammatory or toxic nanoparticles and microparticles, including those made from some forms of silica and asbestos, can lead to pulmonary fibrosis and neoplasia [22], it will be useful to develop nanoparticle scaffolds that do not trigger potentially damaging inflammatory pathways during particle uptake. The uptake of diverse types of nanoparticles and microparticles in the lung by a range of endocytic cell subtypes has recently been extensively reviewed [23]
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