EGCG-Building Nanocarriers for Multitasking Drug Delivery: Design Principles, Therapeutic Opportunities, and...

Recent advances in nanotechnology for drug delivery have enabled improved pharmacokinetics, controlled drug release, and enhanced tissue targeting. However, the clinical impact of many nanocarrier systems remains limited because most carriers exhibit typically low drug loading, resulting in modest therapeutic benefit and concerns related to excipient burden. Conventional nanocarriers are often composed predominantly of pharmacologically inert materials, requiring large carrier doses that may contribute to immune-related effects, undesired tissue accumulation, and manufacturing complexity. Moreover, the traditional drug loading-stability trade-off has long constrained nanocarrier design. These limitations have stimulated increasing interest in therapeutically active carriers, in which the carrier itself contributes to therapeutic efficacy. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, has emerged as a promising molecular building block for such systems. EGCG possesses intrinsic biological activities such as antioxidant, anti-inflammatory, anticancer, and drug resistance-modulating effects. In addition, the polyphenolic structure of EGCG enables diverse molecular interactions, including hydrophobic interaction, π-π stacking, hydrogen bonding, metal coordination, and dynamic boronate-catechol bonding, allowing EGCG to associate with a wide range of therapeutic agents and promote nanoscale assembly in aqueous environments. Through these combined physicochemical and pharmacological properties, EGCG-building nanocarriers integrate structural and therapeutic functions within a single platform. Such systems can achieve relatively high drug loading, reduce reliance on inert excipients, and promote combinational therapeutic effects between carrier and payload, including the modulation of drug resistance pathways. EGCG-building nanocarriers can be constructed either through direct assembly with therapeutic agents or through chemical modification that programs EGCG into hierarchically organized nanostructures. This review provides an up-to-date overview of EGCG-building nanocarriers, highlighting their design principles, nanocarrier architectures, functional advantages, predominantly preclinical and cancer-focused applications, and key challenges for clinical translation.