Supramolecular soft matter in traditional Chinese medicine: multiscale structure–function evidence, critical limitations, and translational challenges
- 1Department of Traditional Chinese Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital
- 2Department of Traditional Chinese Medicine, Peking University Third Hospital
Abstract
Plant metabolites used in traditional Chinese medicine (TCM) can form supramolecular assemblies in decoctions or in formulations prepared from purified molecules. These experimental settings support different conclusions. This narrative review examines TCM-derived supramolecular soft matter (TCM-derived SSM) through relationships among molecular interactions, assembly structure, physicochemical properties, and biological responses. It distinguishes assemblies isolated from decoctions, recombined extracts, formulations prepared from purified metabolites, and mixtures of defined metabolites with extracts. Micelles, vesicles, nanoparticles (NPs), nanofibers (NFs), and supramolecular gels provide examples, while carbonized products and covalently crosslinked carriers are discussed as related materials with distinct formation mechanisms. Selected studies associate morphology, surface chemistry, or deformability with altered delivery and preclinical activity. However, the presence of particles, successful reconstitution, and improved efficacy do not individually establish that an assembly is necessary for the effect of a complete preparation. Our contribution is an evidence-oriented comparison of preparation routes, structural measurements, biological comparisons, and the limits of inference across these preparations. We also examine artificial intelligence (AI)-assisted modeling and candidate critical quality attributes (CQAs) within a Quality by Design (QbD) perspective. Predictive design and assembly-based quality control are presented as research prospects that require reproducible measurements, appropriate controls, and validation across batches and biological settings. Self-assembly is a general physicochemical phenomenon; TCM provides a context for studying defined botanical drug combinations and preparation processes rather than evidence of properties unique to one medical tradition. We position this physical-state perspective within the established literature on synergy, antagonism and pharmacokinetic interactions in botanical mixtures.
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BibTeX
@article{li2026supramolecular,
title = {{Supramolecular soft matter in traditional Chinese medicine: multiscale structure–function evidence, critical limitations, and translational challenges}},
author = {Tianning Li and Baoguang Huang and Xiangyu Wang and Jiacheng Zhang and Yutian Zhu and Siqi Guan and Jingshang Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1945675},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1945675/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Supramolecular soft matter in traditional Chinese medicine: multiscale structure–function evidence, critical limitations, and translational challenges
AU - Tianning Li
AU - Baoguang Huang
AU - Xiangyu Wang
AU - Jiacheng Zhang
AU - Yutian Zhu
AU - Siqi Guan
AU - Jingshang Wang
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1945675
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1945675/full
AB - Plant metabolites used in traditional Chinese medicine (TCM) can form supramolecular assemblies in decoctions or in formulations prepared from purified molecules. These experimental settings support different conclusions. This narrative review examines TCM-derived supramolecular soft matter (TCM-derived SSM) through relationships among molecular interactions, assembly structure, physicochemical properties, and biological responses. It distinguishes assemblies isolated from decoctions, recombined extracts, formulations prepared from purified metabolites, and mixtures of defined metabolites with extracts. Micelles, vesicles, nanoparticles (NPs), nanofibers (NFs), and supramolecular gels provide examples, while carbonized products and covalently crosslinked carriers are discussed as related materials with distinct formation mechanisms. Selected studies associate morphology, surface chemistry, or deformability with altered delivery and preclinical activity. However, the presence of particles, successful reconstitution, and improved efficacy do not individually establish that an assembly is necessary for the effect of a complete preparation. Our contribution is an evidence-oriented comparison of preparation routes, structural measurements, biological comparisons, and the limits of inference across these preparations. We also examine artificial intelligence (AI)-assisted modeling and candidate critical quality attributes (CQAs) within a Quality by Design (QbD) perspective. Predictive design and assembly-based quality control are presented as research prospects that require reproducible measurements, appropriate controls, and validation across batches and biological settings. Self-assembly is a general physicochemical phenomenon; TCM provides a context for studying defined botanical drug combinations and preparation processes rather than evidence of properties unique to one medical tradition. We position this physical-state perspective within the established literature on synergy, antagonism and pharmacokinetic interactions in botanical mixtures.
SN - 1663-9812
ER -