Intracellular Chemical Reaction‐Induced Self‐Assembly for the Construction of Artificial Architecture and Its Functions

Abstract

Intracellular assemblies play vital roles in maintaining cellular functions through structural recognition‐mediated interactions. The introduction of artificial structures has garnered substantial interest in modulating cellular functions via activation/inhibition interactions with biomacromolecules. However, the cellular uptake of these high‐molecular‐weight structures may limit their performance. Recently, intracellular chemical‐reaction‐induced self‐assembly has emerged as a promising strategy for generating in situ nanostructures with biofunctionalities for interacting with biomacromolecules. This approach addresses the challenge of synthetic reactions occurring in complex intracellular environments by utilizing diverse chemical reactions that respond to endogenous and exogenous stimuli. This review provides an overview of the latest advancements in intracellular chemical‐reaction‐induced self‐assembly techniques. It focuses on their responsiveness to specific endogenous conditions, such as redox environments and overexpressed enzymes. Additionally, the initiation of chemical reactions through exogenous stimuli, including chemical reagents and irradiation is explored. Polymerization‐induced hydrophobicity is highlighted, leading to self‐assembly into micro‐/nanostructures. These processes contribute to the in situ construction of synthetic materials with diverse morphologies, offering versatile functionalities for biological applications.

Folic Acid-Functionalized β-Cyclodextrin for Delivery of Organelle-Targeted Peptide Chemotherapeutics in Cancer

“…Further research aims to develop organelle-localized peptide assemblies, where peptide amphiphiles are specifically directed to organelles such as mitochondria, lysosomes, and the endoplasmic reticulum. This targeting allows for the disruption of organelle function through self-assembly, thus initiating cancer cell death. − However, a significant limitation is their low selectivity, similar to conventional chemotherapeutic drugs, owing to their accumulation in the normal tissue . In this context, the administration of the chemotherapeutics/peptide amphiphiles in the form of prodrug/self-assembled prodrugs using various delivery vehicles and host–guest chemistry to release the active parent drugs in situ presents a promising approach to enhance the efficacy and selectivity of the parent drugs/peptide amphiphiles. − …”