Cell membrane biointerfaces for natural product discovery and biomimetic delivery: from affinity screening to nanomedicine.

Abstract

Natural products remain an important source of bioactive molecules, but their translation is often limited by inefficient identification of target-relevant constituents and poor in vivo delivery. Cell membrane-based technologies offer a promising way to address these two challenges through membrane-affinity screening and biomimetic membrane nanocarriers. However, these approaches have usually been developed as separate strategies rather than as connected stages of natural-product translation. In this review, we propose a membrane-centered discovery-to-delivery framework in which cell membranes function as programmable biointerfaces linking upstream compound discovery with downstream nanomedicine design. Cell membrane chromatography and related affinity platforms can preserve disease-relevant receptor contexts and enrich membrane-interacting constituents from complex natural-product mixtures. In parallel, cell membrane-biomimetic nanocarriers can inherit functional membrane components, including proteins, glycans and self-recognition signals, thereby improving circulation, lesion targeting, immune modulation and therapeutic efficacy. We further introduce a "two-membrane, one-target" strategy, in which the screening membrane and delivery membrane do not need to be identical but should be connected by a validated receptor- or interface-level recognition mechanism. By integrating evidence-ranked screening studies with biomimetic delivery systems, this review highlights the importance of distinguishing binding identification, functional validation, in vivo efficacy and translational feasibility. This membrane-centered perspective provides a structured framework for improving the mechanistic rigor and translational potential of natural-product-based nanomedicine.