A synergistic nanotherapy for skin photoaging via self-assembly of epigallocatechin-3-gallate and recombinant human collagen

Abstract

UV-induced skin photoaging is a complex pathology driven by oxidative stress and extracellular matrix (ECM) depletion. Although recombinant human collagen (RHC) and epigallocatechin-3-gallate (EGCG) address these mechanisms, their synergy is limited by RHC’ s poor permeability and EGCG’ s instability. Here, we present a supramolecular co-assembly strategy to overcome these barriers. Validated by molecular dynamics simulations, we utilized the intrinsic proline-rich domains of RHC as anchors for EGCG to construct uniform nanospheres (< 100 nm). This architecture sterically shields EGCG, significantly enhancing stability and reducing cytotoxicity. Biologically, the nanospheres restored mitochondrial membrane potential and promoted anti-inflammatory M2 macrophage polarization. In a photoaging mouse model, the nanospheres outperformed monotherapies, effectively reversing epidermal hyperplasia and restoring the Type I/III collagen ratio. This study resolves the delivery-stability paradox of protein–polyphenol therapeutics, offering a potent strategy for regenerating photodamaged skin.

Graphical Abstract

Keywords

Skin photoaging / Recombinant human collagen / Epigallocatechin-3-gallate / Nanospheres / Supramolecular engineering / Synergistic therapy

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Funding

the Key-Area Research and Development Program of Guangdong Province(No.2022B1111080007)

Guangzhou Key R&D Program(No. 202103030003)

National Natural Science Foundation of China(No. U22A20277, 32170865, and 82071634)

Natural Science Foundation of Guangdong Province(No. 2022A1515012178)

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