Plant-derived nanocarriers & nanostructures for barrier-defined translation: a comprehensive review of mechanisms, targets, and translation

Plant-derived nanocarriers (PDNs) constitute a heterogeneous family of bioinspired delivery platforms, including plant-derived extracellular vesicles, lipid-based nanovectors, and plant viral nanoparticles, that have attracted growing interest for applications in diseases constrained by biological barriers. A critical challenge in this field is distinguishing descriptive reports of barrier interaction from mechanistically and translationally meaningful evidence. This review provides a structured synthesis of plant-derived nanocarriers through a barrier-defined framework, rather than a platform-centric catalog, to clarify where and how these systems may add value relative to established nanomedicine approaches. We examine three exemplar contexts in which delivery barriers dominate therapeutic failure: central nervous system tumors, where the relevant interface is often the blood-tumor barrier rather than an intact blood-brain barrier; metabolic steatotic liver disease, governed by oral exposure and the gut-liver axis; and radiation-induced intestinal injury, characterized by epithelial disruption, oxidative stress, and inflammatory signaling. Across these settings, we differentiate intrinsic bioactivity of plant-derived carriers from engineered payload delivery, and critically assess the experimental models, routes of administration, and readouts used to support claims of tissue access and efficacy. Importantly, we highlight recurring methodological limitations, including heterogeneous isolation workflows, labeling artifacts, and overgeneralization from disease-compromised barriers, and align terminology with current extracellular vesicle reporting guidance. Beyond biological performance, we evaluate translational constraints, including pharmacokinetics, mononuclear phagocyte system clearance, manufacturing scalability, and regulatory classification ambiguity. By integrating mechanistic evidence with barrier context and translational readiness, this review reframes plant-derived nanocarriers not as universally superior delivery systems, but as context-dependent platforms whose utility depends on matching carrier class, route, and disease biology. This synthesis aims to extract actionable design principles while delineating the evidentiary gaps that must be addressed before clinical translation.