国内团队:口服纳米药物协同治疗结肠炎相关结直肠癌
创作:EADGBE 审核:Lexi 2019年12月16日
  • 壳聚糖骨架与丙烯酸反应生成羧乙基团,分别与姜黄素(CUR)和7-乙基-10-羟基喜树碱(SN38)酯化获得nCUR和nSN38纳米结构;
  • nCUR可抑制小鼠巨噬细胞中炎症性细胞因子表达和活性氧产生;
  • nSN38通过增加细胞凋亡抑制大肠癌细胞增生;
  • 口服nCUR主要聚集于结肠炎小鼠的结肠,并增加患病小鼠存活率和减轻症状;
  • nSN38可靶向大肠肿瘤,并在肿瘤组织聚集;
  • nCUR和nSN38协同作用诱导肿瘤细胞周期阻滞和凋亡,从而抑制肿瘤生长。
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Lexi
结肠炎相关结直肠癌(CAC)的有效治疗面临巨大挑战。目前,有相当大的需求开发口服生物可利用剂型,使治疗药物能够安全有效地输送到胃肠道局部病变部位。来自浙江大学医学院的王杭祥和韩卫东研究团队近日在Theranostics杂志发表的一项最新研究,针对炎症性肠病和CAC的协同治疗开发了口服纳米治疗剂。研究结果表明,生物胶壳聚糖材料可用于制备胶体稳定的纳米药物,适用于口服给药。这两种纳米药物在炎症的肠道区域和肿瘤组织中都有大量的积累,对CAC的治疗具有良好的协同作用,值得进一步的临床转化。
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Theranostics [IF:8.579]

Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer

口服递送纳米疗法协同治疗结肠炎相关性结直肠癌

10.7150/thno.38081

2019-10-12, Article

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Purpose: Colitis-associated colorectal cancer (CAC) poses substantial challenges for effective treatment. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the safe and effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract.
Experimental Design: In this study, we developed orally deliverable nanotherapeutics for the synergistic treatment of inflammatory bowel diseases (IBDs) and CAC. Water-insoluble curcumin (CUR) and 7-ethyl-10-hydroxycamptothecin (SN38), which served as anti-inflammatory and cytotoxic agents, respectively, were chemically engineered into hydrophilic mucoadhesive chitosan for the generation of chitosan-drug amphiphiles. Results: The resulting amphiphilic constructs formed core-shell nanostructures in aqueous solutions and were orally administered for in vivo therapeutic studies. Using a preclinical CAC mouse model, we showed that the orally delivered nanotherapeutics locally accumulated in inflamed intestinal regions and tumor tissues. Furthermore, the therapeutic synergy of the combined nanotherapeutics in CAC mice was evaluated. Compared with their individual drug forms, combined CUR and SN38 nanoparticles yielded synergistic effects to alleviate intestinal inflammation and protect mice from ulcerative colitis. Notably, the combinatorial therapy demonstrated a remarkable tumor shrinkage with only ~6% of the total tumors exceeding 4 mm in diameter, whereas ~35% of tumors were observed to exceed a diameter of 4 mm in the saline-treated CAC mice. These data suggest a new and reliable approach for improving the treatment of IBD and CAC.
Conclusions: Our results showed that bioadhesive chitosan materials can be used to produce colloidal-stable nanotherapeutics that are suitable for oral delivery. Both nanotherapeutics exhibited substantial accumulation in inflamed intestinal regions and tumor tissues and showed good synergy for treating CAC, warranting further clinical translation.

First Authors:
Weidong Han

Correspondence Authors:
Weidong Han,Hangxiang Wang

All Authors:
Weidong Han,Binbin Xie,Yiran Li,Linlin Shi,Jianqin Wan,Xiaona Chen,Hangxiang Wang

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