Dual‑targeting nanomicelles with CD133 and CD44 aptamers for enhanced delivery of gefitinib to two populations of lung cancer‑initiating cells

Abstract

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.