Supramolecular assemblies are essential components of living organisms. Cellular scaffolds, such as the cytoskeleton or the cell membrane, are formed via secondary interactions between proteins or lipids and direct biological processes such as metabolism, proliferation and transport. Inspired by nature’s evolution of function through structure formation, a range of synthetic nanomaterials has been developed in the past decade, with the goal of creating non-natural supramolecular assemblies inside living mammalian cells. Given the intricacy of biological pathways and the compartmentalization of the cell, different strategies can be employed to control the assembly formation within the highly crowded, dynamic cellular environment. In this Review, we highlight emerging molecular design concepts aimed at creating precursors that respond to endogenous stimuli to build nanostructures within the cell. We describe the underlying reaction mechanisms that can provide spatial and temporal control over the subcellular formation of synthetic nanostructures. Showcasing recent advances in the development of bioresponsive nanomaterials for intracellular self-assembly, we also discuss their impact on cellular function and the challenges associated with establishing structure–bioactivity relationships, as well as their relevance for the discovery of novel drugs and imaging agents, to address the shortfall of current solutions to pressing health issues.

超分子组装体是生物体的重要组成部分。细胞支架，如细胞骨架或细胞膜，是通过蛋白质或脂质之间的二次相互作用以及直接的生物过程（如代谢、增殖和运输）形成的。受自然界通过结构形成而实现功能进化的启发，过去十年中开发了一系列合成纳米材料，其目标是在活哺乳动物细胞内创建非天然超分子组件。鉴于生物途径的复杂性和细胞的区室化，可以采用不同的策略来控制高度拥挤、动态的细胞环境中的组装形成。在这篇评论中，我们强调新兴的分子设计概念，旨在创建响应内源刺激以在细胞内构建纳米结构的前体。我们描述了可以对合成纳米结构的亚细胞形成提供空间和时间控制的潜在反应机制。展示用于细胞内自组装的生物响应性纳米材料开发的最新进展，我们还讨论了它们对细胞功能的影响和与建立结构-生物活性关系相关的挑战，以及它们与发现新药物和成像剂的相关性，以解决当前紧迫健康问题解决方案的不足。我们描述了可以对合成纳米结构的亚细胞形成提供空间和时间控制的潜在反应机制。展示用于细胞内自组装的生物响应性纳米材料开发的最新进展，我们还讨论了它们对细胞功能的影响和与建立结构-生物活性关系相关的挑战，以及它们与发现新药物和成像剂的相关性，以解决当前紧迫健康问题解决方案的不足。我们描述了可以对合成纳米结构的亚细胞形成提供空间和时间控制的潜在反应机制。展示用于细胞内自组装的生物响应性纳米材料开发的最新进展，我们还讨论了它们对细胞功能的影响和与建立结构-生物活性关系相关的挑战，以及它们与发现新药物和成像剂的相关性，以解决当前紧迫健康问题解决方案的不足。