Department of Pharmacy, Pharmaceutical Biotechnology, Ludwig-Maximilians-Universität Munich, 81377 Munich, Germany.
Center for NanoScience, Ludwig-Maximilians-Universität Munich, 80799 Munich, Germany.
Proc Natl Acad Sci U S A. 2024 Mar 12;121(11):e2307799120. doi: 10.1073/pnas.2307799120. Epub 2024 Mar 4.
Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic RNA during delivery to the target tissue and across cellular membrane barriers and then releasing the cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied in lipoplexes and lipid nanoparticles, over medium-sized sequence-defined xenopeptides, to macromolecular polycations applied in polyplexes and polymer micelles. This perspective highlights the discovery of distinct virus-inspired dynamic processes that capitalize on mutual nanoparticle-host interactions to achieve potent RNA delivery. From the host side, subtle alterations of pH, ion concentration, redox potential, presence of specific proteins, receptors, or enzymes are cues, which must be recognized by the RNA nanocarrier via dynamic chemical designs including cleavable bonds, alterable physicochemical properties, and supramolecular assembly-disassembly processes to respond to changing biological microenvironment during delivery.
载体用于 RNA 的递呈必须是动态的，首先在递送至靶组织和穿过细胞膜屏障的过程中稳定并保护治疗性 RNA，然后以生物活性形式释放货物。载体的化学空间范围从小的阳离子脂质体应用于脂质体和脂质纳米颗粒，到中等大小的序列定义的异肽，再到大分子聚阳离子应用于多聚物和聚合物胶束。本综述重点介绍了不同的受病毒启发的动态过程的发现，这些过程利用纳米颗粒-宿主相互作用来实现有效的 RNA 递呈。从宿主方面来看，pH 值、离子浓度、氧化还原电势、特定蛋白质、受体或酶的存在等细微变化是信号，RNA 纳米载体必须通过包括可裂解键、可改变的物理化学性质以及超分子组装-解组装过程等动态化学设计来识别这些信号，以响应递呈过程中不断变化的生物微环境。
