Targeting lung cancer initiating cells by all‑trans retinoic acid‑loaded lipid‑PLGA nanoparticles with CD133 aptamers

Zhang,Yu; Zhao,Juan; Sun,Jing; Huang,Lu; Li,Qingfeng

doi:10.3892/etm.2018.6762

Targeting lung cancer initiating cells by all‑trans retinoic acid‑loaded lipid‑PLGA nanoparticles with CD133 aptamers

Authors:
- Yu Zhang
- Juan Zhao
- Jing Sun
- Lu Huang
- Qingfeng Li
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Affiliations: Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441000, P.R. China, Department of Pharmacy, Second Military Medical University, Shanghai 200433, P.R. China
Published online on: September 19, 2018 https://doi.org/10.3892/etm.2018.6762
Pages: 4639-4649
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer initiating cells represent a specific subpopulation of lung cancer cells, which significantly contribute to the initiation, metastasis and recurrence of lung cancer. CD133, initially considered a marker of stem cells, is now considered as a marker for lung cancer initiating cells. All‑trans retinoic acid (RA) has been demonstrated to cause the differentiation, inhibition of proliferation, and apoptosis of cancer cells and cancer initiating cells. However, there have been no reports on the activity of RA against lung cancer initiating cells. In the present study, the activity of RA against lung cancer initiating cells was investigated by determining the cytotoxicity, and performing a tumorsphere assay and flow cytometry‑based analysis. In addition, to promote the therapeutic effect of RA in CD133+ lung cancer initiating cells, RA‑loaded lipid poly(lactic‑co‑glycolic acid) (PLGA) nanoparticles with CD133 aptamers (RA‑LPNPs‑CD133) were developed. The activity of RA and RA‑LPNPs‑CD133 against lung cancer initiating cells was also investigated. RA‑LPNPs‑CD133 had a size of 129.9 nm, and exhibited sustained release of RA during the 144‑h period. For the first time, to the best of our knowledge, the present study demonstrated that RA exerted potent activity towards CD133+ lung cancer initiating cells. The results also showed that RA‑LPNPs‑CD133 efficiently and specifically promoted the delivery of RA to CD133+ lung cancer initiating cells, exhibiting superior inhibitory effects against CD133+ lung cancer initiating cells compared with non‑targeted nanoparticles and RA. To the best of our knowledge, the present study is the first to report the promotion of RA delivery via nanoparticles to lung cancer initiating cells and achievement of a superior inhibitory effect against lung cancer initiating cells by the utilization of CD133 aptamers. Therefore, RA‑LPNPs‑CD133 represents a promising tool for the elimination of lung cancer initiating cells.

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