Lung cancer is an aggressive type of cancer that is associated with a high mortality rate. Lung cancer-initiating cells are populations of self-renewing cancer cells with pluripotent differentiation ability. Cancers typically originate from multiple phenotypically distinct cancer-initiating cells. CD133 and CD44 are specific markers that maybe used to distinguish lung cancer-initiating cells. The ability to target a variety of subsets of cancer-initiating cells instead of targeting only one population of cancer initiating-cells has the potential to increase the cancer therapeutic efficacy. In the present study, CD133 and CD44 aptamer-conjugated nanomicelles loaded with gefitinib (CD133/CD44-NM-Gef) were developed to target CD133+ and CD44+ lung cancer-initiating cells. The therapeutic efficacy of CD133/CD44-NM-Gef against lung cancer-initiating cells was assessed by evaluating cell proliferation, tumorsphere formation and detection of CD44+ and CD133+ cells using flow cytometry. The results indicated that CD133/CD44-NM-Gef targeted CD133+ and CD44+ lung cancer-initiating cells and exhibited greater therapeutic efficacy against lung cancer-initiating cells than single-target and non-targeted nanomicelles, suggesting that CD133/CD44-NM-Gef represents a promising treatment for lung cancer by specifically targeting lung cancer-initiating cells. To the best of our knowledge, the present study was the first to report on drug delivery via nanomedicines targeted to multiple populations of cancer-initiating cells using aptamers. As cancer is typically derived from phenotypically distinct cancer-initiating cells, the nanomicelle-based multiple targeting strategy provided is promising for targeting multiple subsets of cancer-initiating cell within a tumor.
Keywords: CD133; CD44; cancer-initiating cell; gefitinib; lung cancer; nanomicelles.
Copyright: © Huang et al.