Fusion of tradition and modernity: Advances in Chinese materia medica self-assembly-driven study on compatibility and processing

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Rooted in Chinese medicine theory, the compatibility and processing of Chinese Materia Medicas (CMMs) have played a vital role in clinical practice for millennia. These practices employ multifaceted approaches such as the Monarch-Minister-Assistant-Guide, the four properties, Qiqing (seven effects), and various processing techniques to enhance therapeutic efficacy, reduce toxicity, improve palatability, and generate novel pharmacological effects. Despite their longstanding history, the global application of CMM remains limited, largely due to an incomplete understanding of the mechanisms underlying compatibility and processing. Recent studies demonstrated that bioactive components in CMM often undergo spontaneous self-assembly, forming nanoscale aggregates through noncovalent interactions. These self-assembled aggregates offer a novel material basis for pharmacological activities, addressing the limitations of traditional decoctions and offering new perspectives for the development and application of CMM formulations. This review compiles and analyzes 121 academic literatures published from 1995 to 2025 that explore the intersection of nanotechnology with CMM compatibility or processing. It outlines the bioactive constituents and mechanisms involved in the formation of CMM self-assembled aggregates. Furthermore, it examines methods for separation and preparation, advanced characterization techniques, and pharmacokinetics/pharmacodynamics of CMM self-assembled aggregates. Focal attention is given to the role of self-assembly involved in enhancing compatibility and processing of CMM. In addition, the environmental impact and sustainability of using self-assembled CMM are also discussed. Finally, the review identifies five unresolved challenges and proposes six future research directions, with the aim of advancing the study of CMM compatibility and processing, and promoting the internationalization, modernization, and precision application of CMM. • By reviewing literatures of Chinese Materia Medica (CMM) self-assembly from 1995 to 2025, compatibility/processing theories were partly clarified. • Summarizing the characterization techniques, active substances, assembly mechanisms, and pharmacokinetics/pharmacodynamics of CMMs. • Five challenges and six future directions on compatibility/processing were proposed.