用于酶向的CpG ODNs传递和增强癌症免疫疗法的甘油素
Huijie Zhang1, Li Lai1, Zhiqing Wang1
1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.
International journal of biological macromolecules
|December 7, 2023
概括
天然糖原纳米颗粒有效地将CpG寡核酸 (ODN) 传递给溶酶体,通过增强抗瘤免疫力和抑制瘤生长而提高癌症免疫疗法,而不会产生毒性.
科学领域:
- 免疫学和纳米医学
- 癌症治疗方法 癌症治疗方法
背景情况:
- CpG寡核酸 (ODN) 激活用于癌症免疫治疗的Toll-like受体9 (TLR9),但遭受快速降解和细胞吸收不良.
- 现有的CpG ODN合成纳米载体存在安全风险和低效的溶酶体释放,阻碍治疗疗效.
研究的目的:
- 开发一种新型,生物相容的纳米导体,用于化体向传递CpG ODNs.
- 通过改善cpgODN传递,保护和释放在溶酶体内来增强癌症免疫疗法.
主要方法:
- 自然糖原与二乙烯二胺 (DETA) 的氨基化产生NH2-Gly纳米颗粒 (约. 40纳米) 的距离.
- 复合CpGODN与NH2-Gly形成纳米导体复合体.
- 对生物相容性,核酶保护,细胞吸收,溶酶体释放 (使用α-葡萄糖酶) 和体内抗瘤疗效的评估.
主要成果:
- NH2-Gly纳米粒子表现出良好的生物相容性和有效复杂的CpG ODN,保护它们免受降解.
- NH2-Gly显著增强了CpG ODNs的细胞吸收,并在溶酶体模仿条件下促进了有效的释放.
- NH2-Gly/CpG复合物触发了强大的抗瘤免疫力,有效地抑制了瘤生长,没有观察到有毒效应或组织损伤.
结论:
- 基于天然糖原的纳米颗粒提供了一个安全有效的平台,用于色素向的CpG ODN的输送.
- 这种方法克服了CpG ODN疗法的关键局限性,显示了精确癌症免疫治疗的重大前景.
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