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 and Nie, Guangjun (2019) Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment. Biomaterials, 216. ISSN 0142-9612

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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
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: LivePure Connector
Date Deposited: 03 Jun 2019 08:30
Last Modified: 12 Sep 2019 14:33
URI: https://ueaeprints.uea.ac.uk/id/eprint/71228
DOI: 10.1016/j.biomaterials.2019.119247

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