Functionalized Coacervates for Cancer Therapy: Advances and Prospects in Phase-Separation-Based Intelligent Drug Delivery.

Functionalized coacervates, a type of nanomaterial inspired by biomolecular condensation, have emerged as an important research direction in biomedicine, particularly in cancer therapy. These membraneless structures formed by liquid-liquid phase separation (LLPS) self-assembly have high drug-loading capacity, favorable biocompatibility, and tunable responsiveness to tumor microenvironment (TME) cues. This programmability enables targeted delivery and controlled release. This review summarizes the latest progress in the design and therapeutic application of functionalized coacervates in cancer therapy. We first introduce the construction strategies, including basic driving forces, material platforms, and advanced architectures. Then, we explain the mechanisms that enhance therapeutic efficacy and reduce toxicity, including enhanced loading and stability, improved pharmacokinetics and tumor accumulation, and enhanced intracellular delivery that can overcome multidrug resistance (MDR). We also discuss spatiotemporal release triggered by TME cues, such as acidity, redox, or enzymatic activity. Next, we highlight applications in chemotherapy, nucleic acid delivery, cancer immunotherapy, multimodal combination therapy, and emerging directions. Finally, we discuss translational challenges and outline future research directions. We aim to provide a coherent framework for researchers and to facilitate the development and clinical translation of coacervate-based therapeutics.