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<p>Oral administration can deliver targeted nanoparticles directly to colorectal cancer (CRC) lesions, bypassing systemic circulation. However, orally administered nanoparticles may become physically entrapped in the small intestine, compromising therapeutic efficacy. To overcome this limitation, we designed and prepared folic acid-modified, CRC cell-targeting nanoparticles (FA/CS/TPP/β-acids) and incorporated them into a sodium alginate hydrogel (Alg/FA/CS/TPP/β-acids). The release of β-acids from the nanoparticles was pH-dependent, with cumulative release following the order: pH 7.8 &gt; pH 6.8 &gt; pH 1.2. The nanoparticle/hydrogel system exhibits good biocompatibility (hemolytic activity &lt; 5%; non-toxic to NCM460 cells) and significantly enhances cellular uptake in HCT116 and HT29 cells. In vivo studies showed that the nanoparticles were non-toxic and effectively inhibited CRC. Interestingly, the hydrogel undergoes a sol-gel transition under acidic gastric conditions (pH 1.2). Upon reaching the colorectum, where the pH is higher, it undergoes a gel-sol transition. These results demonstrate that the alginate-modified hydrogel can protect the nanoparticles in the gastrointestinal environment, enabling targeted release for CRC therapy.</p> Graphical Abstract <p></p>

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In situ sol-gel-sol transformation formed by sodium alginate realizes folic acid-modified chitosan nanoparticles to deliver hops β-acids for colorectal cancer therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月29日

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  • Xia Qiao,
  • Jiayue Liu,
  • Jing Bai,
  • Chao Xu,
  • Qianying Zhao,
  • Songlin Guo,
  • Lu Ding,
  • Duan Ma,
  • Xu Zhang,
  • Bingren Tian

摘要

Oral administration can deliver targeted nanoparticles directly to colorectal cancer (CRC) lesions, bypassing systemic circulation. However, orally administered nanoparticles may become physically entrapped in the small intestine, compromising therapeutic efficacy. To overcome this limitation, we designed and prepared folic acid-modified, CRC cell-targeting nanoparticles (FA/CS/TPP/β-acids) and incorporated them into a sodium alginate hydrogel (Alg/FA/CS/TPP/β-acids). The release of β-acids from the nanoparticles was pH-dependent, with cumulative release following the order: pH 7.8 > pH 6.8 > pH 1.2. The nanoparticle/hydrogel system exhibits good biocompatibility (hemolytic activity < 5%; non-toxic to NCM460 cells) and significantly enhances cellular uptake in HCT116 and HT29 cells. In vivo studies showed that the nanoparticles were non-toxic and effectively inhibited CRC. Interestingly, the hydrogel undergoes a sol-gel transition under acidic gastric conditions (pH 1.2). Upon reaching the colorectum, where the pH is higher, it undergoes a gel-sol transition. These results demonstrate that the alginate-modified hydrogel can protect the nanoparticles in the gastrointestinal environment, enabling targeted release for CRC therapy.

Graphical Abstract