Self-assembled products from natural active compounds: mechanisms and applications in cancer therapy

Natural active compounds (NACs) possess diverse anticancer activities but are often limited by poor aqueous solubility, low bioavailability, insufficient tumor selectivity, and inadequate in vivo stability. Self-assembled products from natural active compounds (SAPNACs) provide a carrier-minimized approach in which NACs directly participate in nanostructure construction, stabilization, or functional organization through non-covalent interactions or metal coordination. Unlike previous reviews that broadly discuss natural-product nanomedicine or carrier-free drug delivery, this review establishes a mechanism-oriented framework for SAPNACs by clarifying their conceptual boundaries and linking molecular features, intermolecular interactions, assembly pathways, physicochemical properties, and anticancer performance. It further distinguishes genuine SAPNACs from conventional carrier-loaded formulations and proposes a classification encompassing pure NAC assemblies, multi-NAC co-assemblies, NAC-drug assemblies, metal ion-mediated systems, protein- or nucleic acid-associated assemblies, and multicomponent hybrids. Their applications in chemotherapy, immunotherapy, phototherapy, magnetic hyperthermia, sonodynamic therapy, herbal therapeutics, and tumor microenvironment regulation are critically evaluated. Key translational barriers, including structural validation, in vivo integrity, pharmacokinetics, biosafety, reproducibility, scalable manufacturing, quality control, and regulatory classification, are also discussed. This framework provides practical criteria for the rational design, evaluation, and clinical development of SAPNAC-based cancer nanomedicines.