期刊
MOLECULES
卷 27, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/molecules27051498
关键词
curcumin; oxaliplatin; hyaluronic acid-zein composite nanoparticles; colorectal cancer; cellular uptake
资金
- Guangdong Province Zhujiang Talent Program, China [2019ZT08H476]
- Shenzhen Science and Technology Program, China [KQTD20180412181334790]
- Innovation Team Project of Universities in Guangdong Province, China [2020KCXTD023]
The potential of CUR-encapsulated hyaluronic acid-zein composite nanoparticles as an oral adjuvant for OXA-based chemotherapy in colorectal cancer has been assessed and shown to have a stronger anticancer effect and reduced side effects.
Curcumin (CUR) has been reported to enhance the chemotherapeutic efficacy of oxaliplatin (OXA) in colorectal cancer (CRC) and inhibit OXA-induced side effects. However, shortcomings, including poor solubility and sensitivity to metabolic transformation, have greatly undermined its value in clinical applications. In this study, the potential of CUR-encapsulated hyaluronic acid (HA)-zein composite nanoparticles (HZ-CUR) as an oral adjuvant for OXA-based chemotherapy was assessed in representative CRC models in mice. Cell viability and colony formation assays in three human CRC cell lines showed that HZ-CUR had a stronger anti-CRC effect than free CUR when given alone and a stronger synergistic effect when combined with OXA, especially in HCT116 and HT29 cell lines. Western blotting, cellular uptake, and RNA interference assays revealed that OXA-induced upregulation of CD44 likely contributed to enhanced cellular uptake of HZ-CUR and thus the enhanced anticancer effect. The significantly improved anti-CRC effects and potential underlying mechanism of HZ-CUR alone and in combination with OXA were further validated in a subcutaneous xenograft and an in situ CRC model in mice. These findings support that HZ-CUR may be an effective oral adjuvant for OXA-based CRC chemotherapy that would not only improve its efficacy but also help reduce the associated side effects.
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