Bioinspired dynamic self-assembling condensates driven by liquid-liquid phase separation for therapeutic system innovation and applications: A review.

Abstract

Liquid-liquid phase separation (LLPS), a key biophysical phenomenon in cellular physiology and pathology, profoundly influences cellular homeostasis and disease progression. Notably, the development of biomimetic intervention strategies based on LLPS principles has emerged as a frontier in disease therapy. This review systematically elucidated the molecular basis and regulatory networks of LLPS, with particular emphasis on its emerging applications in therapeutic development: (1) precise interventions targeting the dynamic properties of pathogenic condensates, offering breakthrough tools for tackling refractory diseases; (2) construction of next-generation responsive delivery platforms by harnessing phase transition and dynamic assembly properties, enabling spatiotemporally precise treatment; and (3) LLPS-powered intelligent biomimetic artificial cells, expanding the boundaries of synthetic biology. We further provided an in-depth analysis of urgent challenges, including decoding of LLPS core mechanisms, the difficulty in selectively distinguishing pathological from physiological condensates, the bottleneck of precise controllability in delivery systems, limited in vivo stability and immunogenicity data of LLPS-based delivery systems, and challenges in engineering controllability and large-scale production. Finally, we outlined potential future research directions, suggesting that integrating LLPS studies with multidisciplinary approaches could provide new strategies and technical support to address these challenges.

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