Synthetic Nanoassemblies for Regulating Organelles: From Molecular Design to Precision Therapeutics

Abstract

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.

Keywords: DNA nanotechnology; dynamic assembly; intracellular assembly; organelle regulation; organelle-targeting; peptide; polymer; precision therapeutics; synthetic nanoassembly.