Plant-derived exosome-like nanoparticles from traditional Chinese medicine herbs: A nanobiological framework for antimicrobial phytochemical delivery

Traditional Chinese Medicine (TCM) has long employed herbs such as ginger (Sheng Jiang, 生姜), turmeric (Jiang Huang, 姜黄), garlic (Da Suan, 大蒜), ginseng (Ren Shen, 人参), licorice (Gan Cao, 甘草), green tea (Lü Cha, 绿茶), and honeysuckle (Jin Yin Hua, 金银花) in classical compound formulations including Yin Qiao San (银翘散), Si Junzi Tang (四君子汤), and Xiao Banxia Tang (小半夏汤) for the treatment of infectious diseases, inflammatory conditions, and gastrointestinal disorders. Emerging evidence now suggests that plant-derived exosome-like nanoparticles (PELNs), nanoscale membranous vesicles naturally produced by these medicinal plants, may constitute a previously unrecognized nanobiological mechanism that underlies and partially explains the therapeutic efficacy attributed to these herbs within the TCM pharmacological system. These nanovesicles, isolated from TCM source plants including Zingiber officinale, Curcuma longa, Allium sativum, Camellia sinensis, and Lonicera japonica, carry a complex cargo of lipids, proteins, plant-specific microRNAs, and potent antimicrobial phytochemicals including gingerols, curcumin, allicin, and epigallocatechin gallate (EGCG). Compared with many synthetic nanocarriers, PELNs have demonstrated favourable biocompatibility, relatively low immunogenicity, partial resistance to gastrointestinal degradation, and potential capability for cross-kingdom biological interactions in experimental studies. This comprehensive review systematically examines the biogenesis, structural architecture, and molecular composition of PELNs, with critical emphasis on their antimicrobial mechanisms including direct membrane disruption, toxin neutralization, phosphatidic acid-mediated selective bacterial uptake, cross-kingdom miRNA gene silencing, immunomodulation via the aryl hydrocarbon receptor pathway, and quorum-sensing inhibition for anti-biofilm applications. Engineering strategies for surface modification, drug co-loading, and pharmacokinetic optimization are evaluated within the context of TCM therapeutic principles. The potential relevance of PELNs in addressing antimicrobial resistance (AMR), particularly against multidrug-resistant pathogens, is critically discussed based on currently available preclinical evidence. Translational challenges encompassing scalability, standardization, stability, safety, and regulatory classification are discussed alongside emerging solutions. Overall, this review positions PELNs as a molecular bridge between classical TCM herbal pharmacology and modern nanomedicine, while emphasizing the significant mechanistic, translational, and regulatory challenges that must be addressed before clinical application.