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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.

journal_name

Exp Ther Med

journal_title

Experimental and therapeutic medicine

authors

Huang X,Wan J,Leng D,Zhang Y,Yang S

doi

10.3892/etm.2019.8220

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

192-204

issue

eissn

1792-0981

issn

1792-1015

pii

ETM-0-0-8220

journal_volume

pub_type

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