Macrophage-Inspired Nanomedicines: Harnessing Innate Biology for Precision Therapy

While conventional nanomedicines often struggle with biological barriers and off-target effects, macrophage-based delivery systems offer a distinct advantage by harnessing the innate homing, barrier-penetrating, and immunomodulatory capacities of these cells. This review provides a critical analysis of the three main platforms derived from this concept: whole-macrophage carriers, macrophage membranes (MM)-coated nanoparticles, and macrophage-derived exosomes. Beyond cataloging engineering strategies-from genetic modification to biomimetic coating-we emphasize the design logic of translating specific biological functions into therapeutic capabilities. A key focus is their application across diverse diseases, particularly in remodeling the tumor microenvironment (TME) and treating inflammatory conditions, where their intrinsic biology aligns with therapeutic goals. Despite promising preclinical outcomes, we argue that the field's central challenge lies in transitioning from proof-of-concept studies to scalable, clinically viable manufacturing processes. This review not only synthesizes current advances but also establishes a framework for evaluating these systems, highlighting the need for standardized characterization and long-term safety studies to guide their rational development toward clinical precision medicine.