Hyperbranched Chain Hybridization for Artificial Aggregates: Prolonging Intracellular Retention for Image-Guided Cellular Fate Modulation

Designing dynamic assemblies in living cells is crucial for creating organelle-like structures, yet precisely controlling their morphological transitions in response to specific signals is a significant challenge. In this study, a DNA framework is combined with hybridization chain reaction (HCR) to achieve specific assembly of hyperbranched aggregates in cancer cells. HCR, distinguished for its signal amplification and linear extension capabilities, enables the morphological transition of precursors to be specifically triggered by trace amounts of endogenous microRNA-21 (miR-21). The spatial constraints of the framework and the diversity of hairpin orientations significantly accelerate the assembly kinetics of hyperbranched networks, and the resulting micrometer-scale aggregates possess enhanced intracellular retention capabilities. Introducing Ce6 molecules as a proof of concept, the regulatory function of aggregates can be activated under light irradiation and remains effective over a long period. The probe we constructed demonstrates good stability and biocompatibility, offers easy functionalization, and works inside cells long-term, making it an ideal candidate material for the construction of organelle-like structures.