Membrane-mediated strategies for efficient intracellular delivery of biologics

Approximately 80% of drugs developed to date are small molecule compounds. While these compounds can effectively inhibit intracellular targets by crossing cell membranes, their efficacy often depends on stringent conditions, such as the presence of a deep hydrophobic pocket for strong binding. Biologics-including peptides, antibodies, and genetic materials-have fewer binding requirements but cannot penetrate cell membranes, limiting their activity to extracellular targets. Notably, the number of intracellular protein and nucleic acid targets is more than four times that of extracellular targets. Given their potential to treat fundamental disease mechanisms, the intracellular delivery of biologics is of critical importance. In this review, we discuss the generation and application of membrane-based carriers, including cell-derived vesicles and artificial membrane-based carriers, with examples categorized by modality to enhance the therapeutic utility of biologics.