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

Xu, Jiaqi, Zhang, Yinlong, Xu, Junchao, Wang, Meifang, Liu, Guangna, Wang, Jing, Zhao, Xiao, Qi, Yingqiu, Shi, Jian, Cheng, Keman, Li, Yao, Qi, Sheng ORCID: https://orcid.org/0000-0003-1872-9572 and Nie, Guangjun (2019) Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment. Biomaterials, 216. ISSN 0142-9612

[thumbnail of Accepted_Manuscript]
Preview
PDF (Accepted_Manuscript) - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (2MB) | Preview

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.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User: LivePure Connector
Date Deposited: 03 Jun 2019 08:30
Last Modified: 19 Dec 2024 00:57
URI: https://ueaeprints.uea.ac.uk/id/eprint/71228
DOI: 10.1016/j.biomaterials.2019.119247

Downloads

Downloads per month over past year

Actions (login required)

View Item View Item