Magnetic Nanocomposites Microparticles (MnMs) for Lung Cancer Treatment via Targeted Pulmonary Delivery

Chemotherapy results in many adverse side effects when administered systemically through oral or intravenous delivery and has shown limited success for the treatment of non-small cell lung cancer (NSCLC).  Localization of this treatment through inhalation therapy can potentially enhance therapeutic response while minimizing side effects [1-3].  Targeted pulmonary delivery facilitates direct, targeted application of bioactive materials to the lungs in a controlled manner.  Certain medical conditions such as asthma and chronic obstructive pulmonary disease (COPD) implement targeted pulmonary delivery as a first line treatment because of its inherent advantages [4].  Such advantages include fast onset of pharmaceutical action [5], higher local concentrations, and reduced systemic side effects.  Further, the treatment of pulmonary diseases with inhalation methods can be improved by avoiding first-pass metabolism of pharmaceutical agents [6].  Traditionally, inhaled therapies consist of small molecule drugs and excipients; however, targeted pulmonary delivery provides a platform for localizing novel nanoparticles to the lungs through direct, topical application [6,7].

Iron oxide (Fe3O4) magnetic nanoparticles (MNPs) have generated considerable interest in biomedicine due to their applicability in drug delivery and their FDA approval as a contrast agent in magnetic resonance imaging (MRI) [8,9].  Additionally, Fe3O4 MNPs have been examined for their potential in targeted pulmonary delivery and have shown negligible pulmonary toxicity for appropriate concentrations [10,11].  One major benefit of using Fe3O4 MNPs is their ability to remotely heat in the presence of an alternating magnetic field providing enhanced control over actuating the onset of therapy [12-14].  In suspension, these MNPs generate heat through frictional (Brownian) and magnetic (Neel) relaxation processes, and the heat generated from these particles can be used to trigger other therapies, increase transport of particles, and induce hyperthermia as a thermal treatment [13,15,16].  

In my CNTC project we are working toward incorporating multifunctional Fe3O4 MNPs into inhalable dry powders composites for the targeted treatment of non-small cell lung cancer (NSCLC) via the pulmonary route.  The heat generated by the Fe3O4 MNPs could be used to increase the transport of the nanoparticles, trigger the onset of therapy, and/or as a form of therapy (hyperthermia).  We are also planning on exploring dual administration of chemotherapy and hyperthermia as this can result in a synergistic effect, and the combination of hyperthermia with targeted pulmonary administration of chemotherapy poses a potential improvement on current cancer treatments. 


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