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Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment

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  • Accepted_Manuscript

    Accepted author manuscript, 2 MB, PDF-document

    Embargo ends: 3/06/20

DOI

Authors

  • Jiaqi Xu
  • Yinlong Zhang
  • Junchao Xu
  • Meifang Wang
  • Guangna Liu
  • Jing Wang
  • Xiao Zhao
  • Yingqiu Qi
  • Jian Shi
  • Keman Cheng
  • Yao Li
  • Sheng Qi
  • Guangjun Nie

Organisational units

Abstract

The acquisition of stemness in colorectal cancer (CRC) attributed to the recurrence and metastasis in CRC treatment. Therefore, targeting the stemness of CRC forms a basis for the development of novel therapeutic approaches. However, the pain and systemic side effect from long-term of venipuncture injection remain great challenges to neoplastic treatment. Here, we introduce an oral drug delivery system for sustained release of BMI-1 inhibitor (PTC209) that reverse the stemness of CRC to over-come these obstacles. In this system, nanoparticles modified with hyaluronic acid (HA) showed high-affinity to CD44 / CD168 overexpressed-CRC cells, and efficiently targeted to tumor site in a metastatic orthotropic colon cancer mouse model by oral administration. Significantly, the observed tumor growth inhibition is accompanied by decreased expression of stemness markers in the tumor tissues. Furthermore, HA-NPs-PTC209 also significantly prevented metastasis to the gastrointestinal system, while failing to exhibit acute side effects. In summary, we have developed an orally active, easily synthesized nanomedicine that shows promise for the treatment of colon cancer.

Details

Original languageEnglish
Article number119247
JournalBiomaterials
Volume216
Early online date3 Jun 2019
DOIs
Publication statusPublished - Sep 2019
Peer-reviewedYes

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