The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH) guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment. 1. Introduction Worldwide lung cancer is the leading cause of cancer-related deaths with a dismal 5-year survival rate of only 15% [1]. Every year in the United States approximately 220,000 individuals are diagnosed with lung cancer of which 85% of the cases are classified as non-small-cell lung carcinoma (NSCLC) [1] while the remaining cases are diagnosed as small-cell lung carcinoma (SCLC). Current treatment strategies are strongly dependent on the type of malignancy and stage at the time of diagnosis but often involve a combination of surgery, chemotherapy, and/or radiation therapy. Chemotherapy, a first-line treatment option for advanced-stage lung cancer, is often administered intravenously where it circulates throughout the body ultimately locating and destroying cancerous and normal tissues. Standard first-line chemotherapy regimens for lung cancer include platinum-based drugs such as cisplatin and carboplatin. However, platinum-based chemotherapy is riddled with dose-limiting side
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