对AIE可视化纳米脂质体的生理反应的ERG/DOTAP调制是由冠状蛋白主导的
Keyi Chen1, Meihong Ding2, Shasha Lu1
1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310035, China.
Colloids and surfaces. B, Biointerfaces
|March 1, 2026
概括
脂质纳米颗粒 (Lips) 与聚合诱导的排放纳米颗粒显示可调节的组织向. 配方调整,包括使用厄戈斯特,通过改变冠状蛋白组成来优化肝脏的分布.
科学领域:
- 纳米医学和药物输送
- 生物材料科学 生物材料科学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 脂质纳米颗粒 (Lips) 由于其生物相容性和可调性特性,是有前途的药物输送系统.
- 在Lips in vivo中形成的蛋白质冠状 (PC) 影响其生物相互作用和组织向.
- 目前追踪Lips in vivo和理解PC介导准的方法是有限的.
研究的目的:
- 开发一个可视化纳米脂质体系统 (R1@Lip) 以追踪Lip in vivo的命运.
- 调查Lip配方对PC成分和随后的组织向的影响.
- 建立R1@Lip配方,PC和组织热带性之间的关系.
主要方法:
- 合成聚合诱导的发射光纳米粒子 (AIEgen R1) 并将它们封装在Lips.
- 准备的R1@Lip配方具有不同的组成,包括胆固醇 (CHOL) 和厄戈斯特醇 (ERG).
- 使用光成像进行量化体内生物分布,并通过蛋白质组学分析PC成分.
主要成果:
- 与基于胆固醇的Lips.com相比,R1@Lip配合厄戈斯特醇 (R1@Lip-4) 的配方显示肝脏向性增强 (55.4%).
- 蛋白质组分析揭示了PC中富含的特定蛋白质与组织热带性相关 (例如,DOTAP含量影响肝脏与肺向蛋白质).
- 埃尔戈斯特替代调节PC组合,有利于向肝脏的蛋白质,减少向肺部的蛋白质.
结论:
- 该研究确立了R1@Lip配方,蛋白质冠状元组成和组织向之间的明确联系.
- 唇部配方,特别是使用厄戈斯特和阴性脂质含量,可以精确调节PC特性.
- 这为提高纳米脂质体的组织向性提供了一种策略,用于药物输送应用.
相关概念视频
Receptor-mediated Endocytosis
Overview
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:


