Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake
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...
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MDPI AG
2022-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/5/1498 |
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| author | Lu Liu Shufang Yang Feng Chen Ka-Wing Cheng |
| author_facet | Lu Liu Shufang Yang Feng Chen Ka-Wing Cheng |
| author_sort | Lu Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:30:27Z |
| format | Article |
| id | doaj.art-c6c1371554c94e2eb0a03b0bbf08206e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T20:30:27Z |
| publishDate | 2022-02-01 |
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| series | Molecules |
| spelling | doaj.art-c6c1371554c94e2eb0a03b0bbf08206e2023-11-23T23:25:14ZengMDPI AGMolecules1420-30492022-02-01275149810.3390/molecules27051498Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular UptakeLu Liu0Shufang Yang1Feng Chen2Ka-Wing Cheng3Institute for Food and Bioresource Engineering, College of Engineering, Peking University, Beijing 100871, ChinaShenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, ChinaShenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, ChinaShenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, ChinaCurcumin (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.https://www.mdpi.com/1420-3049/27/5/1498curcuminoxaliplatinhyaluronic acid–zein composite nanoparticlescolorectal cancercellular uptake |
| spellingShingle | Lu Liu Shufang Yang Feng Chen Ka-Wing Cheng Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake Molecules curcumin oxaliplatin hyaluronic acid–zein composite nanoparticles colorectal cancer cellular uptake |
| title | Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake |
| title_full | Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake |
| title_fullStr | Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake |
| title_full_unstemmed | Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake |
| title_short | Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake |
| title_sort | hyaluronic acid zein core shell nanoparticles improve the anticancer effect of curcumin alone or in combination with oxaliplatin against colorectal cancer via cd44 mediated cellular uptake |
| topic | curcumin oxaliplatin hyaluronic acid–zein composite nanoparticles colorectal cancer cellular uptake |
| url | https://www.mdpi.com/1420-3049/27/5/1498 |
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