Targeted Coacervates Enabled by Polyphenol–Peptide Networks for Therapeutic Delivery
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2026
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Journal of the American Chemical Society
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American Chemical Society
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Journal Article
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Jiang, L., Song, Q., Lin, Z., Liu, H., Chen, J., Zhang, X., Li, H., Cortez-Jugo, C., Zhou, J., Liu, L., Caruso, F. & Jiang, H. (2026). Targeted Coacervates Enabled by Polyphenol–Peptide Networks for Therapeutic Delivery. Journal of the American Chemical Society, 148 (22), pp.23293-23304. https://doi.org/10.1021/jacs.6c06722.
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This item is embargoed and will be available on 2027-05-26.
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Abstract
Precise intracellular delivery remains a critical barrier to the efficacy of therapeutic biomolecules. Coacervates, with their high loading capacity, have emerged as a transformative drug delivery platform that can facilitate the intracellular delivery of diverse therapeutic cargos but are limited by poor stability, nonspecific cellular internalization, and uncontrolled release. Herein, we report a simple and versatile surface-engineering strategy that improves the stability of coacervates and enables programmable cell targeting and precise intracellular delivery. Peptide coacervates (PCs) designed with programmable release were coated with polyphenol–peptide networks (PC@PPNs) to encapsulate diverse cargos, including fluorophores, toxic proteins, pro-apoptotic peptides, and plasmid DNA. The dual pH- and glutathione-responsive disassembly of PC@PPNs facilitates endosomal escape and enables controlled cytosolic release. Notably, the association of PC@PPNs with specific cells can be readily programmed by modulating the peptide sequence on PPNs. For example, incorporating HER2-targeting peptides increases the specific association of PC@PPNs with SKOV3 cells from 14% to 75%. The cell-specific targeting is further validated in vivo, as demonstrated by a pronounced size reduction in HER2-overexpressing tumors. This work establishes a rational framework for engineering functional coacervates, advancing their development as versatile and programmable platforms for intracellular delivery.