红细胞膜伪装的减少响应的聚乙烯胺基纳米颗粒用于增强抗瘤效率的反意义寡核酸
Shuang Yang1,2, Beibei He1,3, Cuiping He1,3
1Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
Molecular pharmaceutics
|July 29, 2025
概括
一种新型的红细胞膜伪装输送系统 (R-TSP/AO) 能够有效地输送反感性寡核酸 (AO) 用于瘤治疗. 该系统表现出强大的抗瘤作用和高安全性,克服了AO药物输送当前的局限性.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 药物输送系统 药物输送系统
背景情况:
- 反感性寡核酸 (AO) 对癌症治疗具有前景,但需要高效和安全的输送系统.
- 目前的AO传递方法在向癌细胞和实现治疗疗效方面面临挑战.
- 开发先进的载体对于释放AO在瘤学中的全部潜力至关重要.
研究的目的:
- 为增强瘤治疗设计和开发一种新,安全和高效的AO输送系统.
- 使用改性聚乙烯胺 (PEI) 和红细胞囊泡,创建一个仿生纳米载体.
- 评估开发的AO输送系统的物理化学性质,体外*性能和体内*抗瘤疗效.
主要方法:
- 合成TPGS-SS-PEI通过通过二硫化物键将TPGS与PEI结合.
- 通过在红细胞膜囊泡 (RVs) 中封装带有AO的小粒 (TSP/AO) 来构建R-TSP/AO.
- 标志着R-TSP/AO粒子大小,泽塔潜力,稳定性和*in vitro*转染/基因沉默效率;评估了*in vivo*瘤抑制和小鼠模型中的系统毒性.
主要成果:
- R-TSP/AO的粒子大小为109.7 nm,而泽塔电位为-24.10 mV.
- 该系统表现出对降低条件的敏感性,卓越的稳定性和高安全性 *in vitro*.
- 与未经修改的PEI (*P*<0.001) 相比,R-TSP/AO显示出明显更高的AO转染和基因沉默效率,并且在没有全身毒性的小鼠中实现了55.65%的瘤抑制.
结论:
- 开发的R-TSP/AO系统是基于AO的癌症治疗的安全有效的载体.
- 用红细胞膜进行生物模拟伪装可以增强AO传递和抗瘤功效.
- 在未来的研究中,R-TSP具有作为核酸药物输送的有希望的纳米载体的潜力.
相关概念视频
01:24Modified-Release Drug Delivery Systems: Site-Targeted
Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...