Engineered cellular drug delivery: Strategies and applications.

Cell-based drug delivery systems (CDDS) offer advantages like biocompatibility and tissue homing. However, it faces challenges owing to the complex physiological environment in the body during drug transport, such as the inhibitory immune microenvironment of tumors and the highly selective blood-brain barrier. Additionally, CDDS has limitations, including poor targeting and uncontrolled drug release. Engineered cellular drug delivery systems (ECDDS) have emerged to overcome these hurdles, providing enhanced target specificity, improved barrier crossing, and precise drug release mechanisms. Customizable through chemical and bioengineering strategies, ECDDS represent a versatile platform for precision medicine. While numerous reviews exist on living cell delivery systems, a focused analysis of ECDDS remains limited. This review bridges that gap by offering a comprehensive analysis of contemporary engineering methods and design approaches for ECDDS. We further examine the in vivo fate of these systems and their applications in therapy, imaging, and diagnosis. Importantly, we propose a unified "three-axis" design framework-spanning carrier biology, drug properties, and tissue microenvironment-to guide the rational development of future ECDDS.