响应lysyl氧化酶的定纳米颗粒用于调节瘤免疫微环境
Jinwon Park1, Jung Suk Kim1, Geon Yang1
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
概括
新的纳米颗粒对瘤中的lysyl氧化酶 (LOX) 产生反应,对原进行定,并使近红外除成为可能. 这种方法调节瘤免疫微环境,增加细胞毒性T细胞,并在临床前模型中改善存活率.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 癌症研究 癌症研究
背景情况:
- lysyl氧化酶 (LOX) 稳定了瘤细胞外基质.
- 瘤微环境的相互作用对于癌症的进展和治疗反应至关重要.
研究的目的:
- 设计和评估用于向药物输送和瘤切除的响应LOX的纳米粒子.
- 研究这些纳米粒子在瘤微环境中的免疫调节作用.
主要方法:
- 开发了可响应LOX.的原蛋白涂层的,含有imiquimod的聚多巴胺纳米颗粒 (CPN/IQ).
- 用LOX分泌CT26细胞进行体外研究,以评估纳米粒子定.
- 在CT26瘤携带小鼠体内研究,以评估抗瘤疗效,免疫调节和存活率.
主要成果:
- CPN/IQ纳米颗粒以LOX-依赖的方式固定在原基质上.
- 单次给予CPN/IQ与近红外辐射导致了原发性瘤消去.
- 在初级瘤中,CPN/IQ治疗减少了调节性T细胞 (Tregs) 和增加了细胞毒性CD3+CD8+T细胞.
- 在瘤再挑战模型中,CPN/IQ治疗增强了脏树突细胞成熟,并促进了长期存活.
结论:
- 响应LOX的纳米粒子提供了一个可行的策略来调节瘤免疫微环境.
- 这种纳米粒子系统显示了向瘤切除和诱导全身抗瘤免疫力的潜力.
- 响应LOX的原基质定纳米颗粒的概念可能适用于各种LOX丰富的瘤类型.
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