[A new interpretation of complex pharmacology of traditional Chinese medicine (TCM):as an ideal form of effective substances of TCM, formula-derived nanoparticles(FDN) can achieve multi-level three-dimensional targeted regulation of dynamic disease network].
摘要
An important discovery in recent studies of traditional Chinese medicine(TCM) formulas is that effective components in TCM are typically not present as free monomers, but rather tend to self-assemble into supramolecular nanoaggregates(SANs) or exosome-like nanoparticles(ELNs) to exert combinatorial pharmacological effects. Based on TCM formula theory, modern nanoscience and technology, and emerging pharmaceutical manufacturing techniques, this paper proposes and defines the concept of formula-derived nanoparticles(FDNs). FDNs refer to the ordered nano-scale aggregates spontaneously formed through non-covalent interactions by the inherent active components or nano-scale particles of TCM formulas and their decoction pieces or crude herbs during processing, extraction, purification, preparation, and during in vivo absorption and distribution. FDNs mainly include TCM exosomes(TCM-EXO), TCM decoctosomes(TCM-Deco), TCM carbon quantum dots(TCM-CDs), and TCM bencaosomes(TCM-Benc). At the nanoscale, FDNs exhibit novel physical, chemical, and biological properties and may serve as ideal carriers for the delivery and signal transduction of full-component/multi-component pharmacodynamic substances in TCM formulas. They not only improve bioavailability, enhance drug targeting, and enable multi-component synergistic therapy, but also, owing to their unique "structure-function" hierarchies and multi-scale structural synergy, FDNs can achieve multi-level three-dimensional targeted regulation of complex dynamic disease networks, from "point(key targets)-line(signaling pathways)-plane(hub nodes)-system(disease networks)". This forms a systemic response mechanism for FDN-disease network interaction characterized by "multi-layer regulation"-"pharmacodynamic integration"-"moderate intervention", providing a novel perspective for understanding the mechanisms of TCM in preventing and treating complex diseases. It also offers new strategies