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

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

Research output: Contribution to journalArticle

7 Scopus citations

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 reverses the stemness of CRC to overcome 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.

Original languageEnglish (US)
Article number119247
JournalBiomaterials
Volume216
DOIs
StatePublished - Sep 2019

Keywords

  • Colorectal cancer
  • Oral drug delivery
  • PTC209
  • Stemness

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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