# Metformin-loaded J-AuPPS for infected diabetic wound treatment

**Authors:** Fuli Yin, Lingkai Yang, Haojie Shan, Yuange Li, Yongfeng Zhou, Xiaowei Yu

PMC · DOI: 10.3389/fbioe.2026.1753425 · Frontiers in Bioengineering and Biotechnology · 2026-02-19

## TL;DR

This paper introduces a new nanomaterial that combines metformin and gold-porphyrin structures to treat infected diabetic wounds more effectively.

## Contribution

The development of a multifunctional nanoplatform, Met@J-AuPPS, for synergistic antibacterial and pro-angiogenic wound healing.

## Key findings

- Met@J-AuPPS shows strong antibacterial activity against MRSA and ESBL E. coli, including biofilms.
- NIR-triggered metformin release promotes angiogenesis and tissue repair in diabetic wound models.
- The nanoplatform significantly improves therapeutic outcomes in infected diabetic rat wounds.

## Abstract

Infected diabetic wounds pose a significant clinical challenge owing to the complex wound microenvironment. Various multifunctional synergistic therapeutic nanomaterials have been successfully developed to treat diabetic infected wounds.

A Janus Au–porphyrin polymersome heterostructure loaded with metformin (Met@J-AuPPS) is constructed and presented.

Porphyrin polymersome vesicles loaded with metformin (Met@PPS) was synthesized by supramolecular polymerization enhanced self-assembly. Metformin-loaded Janus gold-porphyrin polymersome (Met@J-AuPPS) was synthesized by photocatalytic synthesis method. Transmission electron microscope (TEM), scanning electron microscope (SEM), UV-vis absorption spectrum and ELISA experiment were used to detect the morphology, structure, photothermal properties and drug release properties of Met@J-AuPPS. The effects of Met@J-AuPPS on the proliferation and activity of HUVECs were detected by CCK-8 test, scratch test, Transwell test and tube formation test. The antibacterial and antibiofilm abilities of Met@J-AuPPS were detected by blood plate test, crystal violet staining, SEM of biofilm and bacterial live/dead staining. Imaging and histological staining were used to detect the efficacy of Met@J-AuPPS in treating diabetic wound infections in vivo.

Excellent photothermal antibacterial performance against gram-positive methicillin-resistant Staphylococcus aureus (MRSA), gram-negative extended-spectrum β-lactamases Escherichia coli (ESBL E. coli), and MRSA/ESBL E. coli biofilm is demonstrated by a strong non-centrosymmetric near-field enhancement (NFE) effect between Met@PPS and Au nanoparticles. Furthermore, the release of metformin under near-infrared (NIR) light promotes angiogenesis and tissue repair. The results therefore show that Met@J-AuPPS exhibits excellent antibacterial/biofilm and pro-angiogenic performance, with significantly enhanced therapeutic effects in infected wounds of diabetic rat models.

This study presents an innovative therapeutic strategy for diabetic wound infections and demonstrates that Met@J-AuPPS has potential as a multifunctional and upgradeable nanoplatform for further biomedical applications.

## Linked entities

- **Chemicals:** metformin (PubChem CID 4091)
- **Species:** Staphylococcus aureus (taxon 1280), Escherichia coli (taxon 562), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Pecam1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 29583] {aka CD31, Pecam}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, ESBL [NCBI Gene 13906541], YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}
- **Diseases:** Cytotoxicity (MESH:D064420), diabetic infected wounds (MESH:D014946), cancer (MESH:D009369), Diabetes (MESH:D003920), Infected (MESH:D007239), hyperglycemic (MESH:D006944), impaired physical activity (MESH:D059445), hyperglycemia (MESH:D006943), inflammation (MESH:D007249), foot wounds (MESH:D014947), DFU (MESH:D017719), MRSA (MESH:D013203), skin defect (MESH:D012868), metabolic disease (MESH:D008659), spectrum beta-lactamases (MESH:C579922), Bacterial infection (MESH:D001424), type II diabetes (MESH:D003924)
- **Chemicals:** pentobarbital sodium (MESH:D010424), polymer (MESH:D011108), TMS (MESH:D013932), carbon (MESH:D002244), HAuCl4 (MESH:C024568), Ti (MESH:D014025), PTFE (MESH:D011138), Zinc (MESH:D015032), CCK- (MESH:D002766), PI (MESH:D010716), mercury (MESH:D008628), Au (MESH:D006046), saline (MESH:D012965), H&amp;E (MESH:D006371), Crystal violet (MESH:D005840), silicon (MESH:D012825), DMF (-), Porphyrin (MESH:D011166), blood glucose (MESH:D001786), DMSO (MESH:D004121), Methicillin (MESH:D008712), glucose (MESH:D005947), ethanol (MESH:D000431), J (MESH:C000608249), H (MESH:D006859), acetic acid (MESH:D019342), PBS (MESH:D007854), silver (MESH:D012834), 5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (MESH:C051232), glutaraldehyde (MESH:D005976), STZ (MESH:D013311), N,N-dimethylformamide (MESH:D004126), paraformaldehyde (MESH:C003043), polystyrene (MESH:D011137), Met (MESH:D008687), water (MESH:D014867), CCK-8 (MESH:D012844)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Staphylococcus aureus (species) [taxon 1280], Rattus norvegicus (brown rat, species) [taxon 10116], Escherichia coli (E. coli, species) [taxon 562]
- **Cell lines:** DWLL205-0010 — Homo sapiens (Human), Werner syndrome, Finite cell line (CVCL_T352), HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959), ATCC35218 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

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## Figures

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## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960594/full.md

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Source: https://tomesphere.com/paper/PMC12960594