Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, College of Chemistry and Materials, Fudan University, Shanghai 200438, P.R. China.
Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P.R. China.
ACS Nano. 2024 Nov 5;18(44):30224-30246. doi: 10.1021/acsnano.4c10194. Epub 2024 Oct 23.
Each organelle referring to a complex multiorder architecture executes respective biological processes via its distinct spatial organization and internal microenvironment. As the assembly of biomolecules is the structural basis of living cells, creating synthetic nanoassemblies with specific physicochemical and morphological properties in living cells to interfere or couple with the natural organelle architectures has attracted great attention in precision therapeutics of cancers. In this review, we give an overview of the latest advances in the synthetic nanoassemblies for precise organelle regulation, including the formation mechanisms, triggering strategies, and biomedical applications in precision therapeutics. We summarize the emerging material systems, including polymers, peptides, and deoxyribonucleic acids (DNAs), and their respective intermolecular interactions for intercellular synthetic nanoassemblies, and highlight their design principles in constructing precursors that assemble into synthetic nanoassemblies targeting specific organelles in the complex cellular environment. We further showcase the developed intracellular synthetic nanoassemblies targeting specific organelles including mitochondria, the endoplasmic reticulum, lysosome, Golgi apparatus, and nucleus and describe their underlying mechanisms for organelle regulation and precision therapeutics for cancer. Last, the essential challenges in this field and prospects for future precision therapeutics of synthetic nanoassemblies are discussed. This review should facilitate the rational design of organelle-targeting synthetic nanoassemblies and the comprehensive recognition of organelles by materials and contribute to the deep understanding and application of the synthetic nanoassemblies for precision therapeutics.
每个细胞器都指代一个复杂的多层次结构，通过其独特的空间组织和内部微环境执行各自的生物学过程。由于生物分子的组装是活细胞的结构基础，因此在活细胞中创建具有特定物理化学和形态特性的合成纳米组装体以干扰或与天然细胞器结构偶联，在癌症的精准治疗中引起了极大关注。在这篇综述中，我们概述了用于精确细胞器调节的合成纳米组装体的最新进展，包括形成机制、触发策略以及在精准治疗中的生物医学应用。我们总结了新兴的材料体系，包括聚合物、肽和脱氧核糖核酸 (DNA) ，以及它们在细胞间合成纳米组装体中的各自分子间相互作用，并强调了它们在构建针对复杂细胞环境中特定细胞器的合成纳米组装体的前体中的设计原则。我们进一步展示了针对特定细胞器（包括线粒体、内质网、溶酶体、高尔基体和细胞核）的开发的细胞内合成纳米组装体，并描述了它们在细胞器调节和癌症精准治疗中的潜在机制。最后，讨论了该领域的关键挑战和未来用于合成纳米组装体的精准治疗的前景。这篇综述应该有助于合理设计靶向细胞器的合成纳米组装体，并促进材料对细胞器的全面认识，有助于深入理解和应用合成纳米组装体进行精准治疗。
