An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells

Zhou, Gang; Bae, Sarah Da Won; Nguyen, Romario; Huo, Xiaoqi; Han, Shuanglin; Zhang, Zhiqiang; Hebbard, Lionel; Duan, Wei; Eslam, Mohammed; Liddle, Christopher; Yuen, Lawrence; Lam, Vincent; Qiao, Liang; George, Jacob

doi:10.1016/j.canlet.2020.12.022

Cited by 45 publications

(23 citation statements)

References 38 publications

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“…It has been reported that several surface markers including CD133, CD90, CD13, CD24, and EpCAM were used to isolate the CSCs from HCC. 46–50 However, the exact biomarkers of CSCs and how they participated in the biological functions of CSCs in HCC is still unclear. The transcription factor Nanog is reported to contribute to maintain the stemness features of embryonic stem cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of SIRT1 Limits Self-Renewal and Oncogenesis by Inducing Senescence of Liver Cancer Stem Cells

Wang¹,

Chen²,

Shen³

et al. 2021

JHC

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Purpose Cancer stem cells (CSCs) have been considered involving in tumorigenesis, local recurrence, and therapeutic drug resistance of hepatocellular carcinoma (HCC). To investigate novel and effective methods for targeting hepatic CSCs is crucial for a permanent cure of liver cancer. Methods The expression level of SIRT1 was detected in CSCs of HCC tissues and cancer cell lines. Expression of CSC markers, the self-renewal and tumorigenic ability of liver CSCs were analyzed with SIRT1 inhibition. Cellular senescence-related markers were used to detect CSCs senescence after inhibition of SIRT1. Results SIRT1 was highly expressed in CSCs of HCC cell lines and human HCC tissues. In vitro study revealed that decreasing of SIRT1 level significantly downregulated the stemness-associated genes of liver CSCs and reduced the CSC stemness properties. Also, downregulated SIRT1 suppressed liver CSCs proliferation by decreasing their self-renewal abilities. Furthermore, CSCs with decreased SIRT1 expression showed limited tumorigenicity and formed smaller HCC tumor in vivo. And SIRT1 decreased CSCs became more susceptible to chemotherapeutic drugs. Mechanistically, SIRT1 decreased CSCs became senescence through the activation of p53-p21 and p16 pathway. The data further indicated that the tumor formed from SIRT1-knockdown CSCs exhibited higher senescence-associated β-galactosidase (SA-β-Gal) activity but lower proliferative capacity. Conclusion Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Inhibition of SIRT1 Limits Self-Renewal and Oncogenesis by Inducing Senescence of Liver Cancer Stem Cells

Wang¹,

Chen²,

Shen³

et al. 2021

JHC

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“…Aptamers have been raised either for CSC-specific targets such as CD133, also known as prominin-1, 77 or for tumor cell-surface markers highly expressed in various cancer types on both CSCs and non-stem cells such as the TfR, CD44, and EpCAM. 78 With the use of an aptamer against CD133, Qiao and others 79 have recently shown that doxorubicinloaded aptamers (CD133-apt-Dox) can selectively deliver Dox into hepatic CSCs, inhibiting proliferation and diethyl nitrosamineinduced tumor growth in an immunocompetent mice model. Several aptamers have been selected to EpCAM, [80][81][82] with one demonstrating similar results to the CD133 A15 aptamer used by Xiang et al 21 in an in vivo model of colon cancer.…”

Section: Targeting Cscsmentioning

confidence: 99%

Aptamers: Cutting edge of cancer therapies

et al. 2021

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“…Examples of the targetable cancer stem cell-specific markers are EpCAM, BORIS sf6, CD133, and DNAJB8 [6]. While some cancer stem cell markers, particularly EpCAM and CD133, have shown promising aptamer-based targetability [15,17,18], others are still subjected to investigation for potential application in aptamer targeting. Cell targeting by means of ligand-decorated nanocarriers is not a new drug delivery strategy and research platform.…”

Section: Expert Opinionmentioning

confidence: 99%

“…In recent years, aptamers (short single-stranded oligonucleotides) have emerged as promising non-protein ligands for cancer stem cell targeting [17]. The aptamers fold into unique tertiary structures and bind to their targets with a high affinity and specificity.…”

Section: Introductionmentioning

confidence: 99%

Targeting genetic tool for long non-coding RNA of cancer stem cells with aptamer-guided nanocarriers

Zaiki

Wong

2021

Expert Opinion on Drug Delivery

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An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells

Cited by 45 publications

References 38 publications

Inhibition of SIRT1 Limits Self-Renewal and Oncogenesis by Inducing Senescence of Liver Cancer Stem Cells

Inhibition of SIRT1 Limits Self-Renewal and Oncogenesis by Inducing Senescence of Liver Cancer Stem Cells

Aptamers: Cutting edge of cancer therapies

Targeting genetic tool for long non-coding RNA of cancer stem cells with aptamer-guided nanocarriers

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