Advances in Antitumor Therapy using Phase-Separated Condensates as Drug Delivery Systems

Although numerous therapeutics show great potential in anti-tumor therapy, their clinical translation is severely hindered by their susceptibility to degradation, poor tissue penetration, and the biocompatibility limitations of traditional vehicles. Consequently, developing advanced delivery systems remains an urgent challenge. Liquid-liquid phase separation (LLPS) drives the formation of micron-sized, membraneless compartments through non-covalent interactions, resulting in high dynamic reversibility and fluid-like behavior to regulate complex intracellular biochemical processes. Capitalizing on these fundamental principles of LLPS, recent research has yielded biomolecular condensates with highly controllable compositions, properties, and functionalities. As delivery vehicles, these phase-separated condensates offer biocompatibility, stimuli responsiveness, dynamic regulatory capabilities, and a unique capacity for multi-targeted co-delivery, opening a transformative paradigm for drug delivery. This review highlights two primary applications of phase-separated condensates in oncology: first, the intrinsic antitumor efficacy of the condensates themselves and their synergistic effects when they are co-loaded with chemotherapeutics; second, their utility as smart platforms for targeted drug delivery, including advanced formulation technologies and therapeutic outcomes. Ultimately, this article systematically reviews progress in the use of LLPS-based condensates as next-generation smart drug delivery systems, providing critical insights for broader drug delivery and nanomedicine communities.