Title

Jigsaw Puzzle-Designed Polyphenol-Macromolecular Supramolecular Networks for Noninvasive Therapy of Deep-Tissue Oral Disease

Research Background

Oral mucosal delivery of macromolecular drugs features noninvasive administration and circumvention of first-pass metabolism, yet it is hindered by two major obstacles: tight mucosal barriers and high enzymatic activity. Existing delivery strategies often show compromises in penetration efficiency, biocompatibility or drug-loading versatility. Developing universal delivery platforms capable of overcoming multiple barriers and accommodating diverse macromolecular agents represents a key challenge in biopharmaceutics.

Research Design

This work establishes a modular “jigsaw-puzzle” nanoplatform (PMIL). Taking advantage of the multivalent noncovalent interactions of green tea polyphenol EGCG, the platform acts as a universal adaptor to co-assemble biologically distinct macromolecules (nucleic acids, proteins, etc.) with ionic liquids into stable nanostructures. The investigation follows a clear logical pipeline: molecular design, assembly validation, model evaluation and mechanistic exploration. Combining computational prediction and experimental characterization, the system is systematically validated in a periodontitis model for its capacities in tissue penetration, anti-inflammation, osteogenic activity and microbiota modulation.

Commentary on the Work

The highlight lies in this highly integrated and synergistic delivery strategy. This “all-in-one” design addresses penetration, stabilization, therapeutic action and microenvironment regulation within a single platform, conveying prominent novelty. The proposed supramolecular assembly concept based on polyphenols, macromolecules and ionic liquids possesses good scalability, offering new insights for other mucosal or local delivery systems. Further studies may focus on its long-term safety and the feasibility of large-scale fabrication.

Journal Source

ACS Nano

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17768014569 (Dr.Gao)

17761925168 (Dr. Zhang)

18013729810 (Dr. Yang)