# Bimetallic Nanozymes/Polypyrrole/Methylene Blue Platform for Photothermal and Catalytic Biofilm Disruption and Angiogenesis Enhancement in Diabetic Wound Healing

**Authors:** Prafful P. Kothari, Tonmoy Banerjee, Balaram Ghosh, Swati Biswas

PMC · DOI: 10.1002/smsc.202500445 · Small Science · 2026-02-03

## TL;DR

A new nanocomposite platform effectively kills antibiotic-resistant bacteria and promotes wound healing in diabetic wounds by combining photothermal and catalytic effects.

## Contribution

A bimetallic nanozyme system with polypyrrole and methylene blue is developed for synergistic biofilm disruption and wound healing.

## Key findings

- CeZn@PPY@MB nanoflowers show strong MRSA biofilm disruption and antibacterial activity.
- The nanocomposite promotes angiogenesis and tissue regeneration in diabetic wound models.
- Photothermal and catalytic effects synergistically enhance wound healing and reduce inflammation.

## Abstract

Diabetic wounds pose a significant challenge due to impaired tissue regeneration, prolonged inflammation, poor oxygen supply, and microbial infections. Methicillin‐resistant Staphylococcus aureus (MRSA) infections delay healing by prolonging inflammation and increasing antimicrobial resistance. To develop an effective antibiotic alternative, multifunctional nanocomposites, ceria‐zinc nanoflowers (CeZn@PPY@MB NFs) bearing a polypyrrole (PPY) coating loaded with methylene blue (MB) are developed, to address the multifaceted requirements for healing diabetic wounds. Due to the synergistic effects of photothermal, catalysis, and reactive oxygen species (ROS) generation,CeZn@PPY@MB NFs exhibit robust antibacterial activity with high collagen deposition and angiogenesis. The nanoflowers, with a high surface area of water lily‐like morphology, are confirmed through scanning electron microscopy, energy‐dispersive X‐ray analysis, X‐ray photoelectron spectroscopy, and X‐ray diffraction analysis. PPY/MB‐mediated synergistic photothermal effect, ROS generation, and catalytic activities lead to robust MRSA killing and biofilm disruption. Nanoflowers demonstrate rapid wound healing due to reduced inflammation, tissue regeneration, and angiogenesis in the diabetes‐induced wound model by modulating tumor necrosis factor‐α, CD‐44, Ki‐67, collagen deposition, ROS, interleukin‐1β (IL‐1β), IL‐8, and IL‐6 expression. Therefore, the developed multifunctional hybrid‐metallic nanoflowers provide an advanced nanotherapeutic platform to eradicate MRSA effectively, offering a promising alternative to antibiotic therapy for managing resistant bacteria‐infected diabetic foot ulcers.

The bimetallic ceria‐zinc nanoflowers coated with polypyrrole and loaded with methylene blue disrupt methicillin‐resistant Staphylococcus aureus biofilms synergistically, promote angiogenesis, thereby achieving efficient diabetic wound healing. Integrated photothermal therapy optimized, photodynamic therapy enhanced, pH‐mediated multifunctional nanozyme catalysis effect for targeted bacterial eradication and tissue regeneration, thus provides a potentially versatile antibiotic‐free therapeutic strategy for managing recalcitrant infections in impaired wounds.© 2026 WILEY‐VCH GmbH

## Linked entities

- **Proteins:** CD44 (CD44 molecule (IN blood group)), Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Chemicals:** methylene blue (PubChem CID 4139), ceria (PubChem CID 73963), zinc (PubChem CID 23994)
- **Species:** Staphylococcus aureus (taxon 1280)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Got2 (glutamic-oxaloacetic transaminase 2) [NCBI Gene 25721] {aka ASPATA, mAAT}, Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Fn1 (fibronectin 1) [NCBI Gene 25661] {aka FIBNEC, fn-1}
- **Diseases:** hypoxia (MESH:D000860), Hemolysis (MESH:D006461), hyperthermia (MESH:D005334), hypoxic (MESH:D002534), microbial infections (MESH:D015163), phototoxicity (MESH:D017484), vascular insufficiency (MESH:D065666), cancerous (MESH:D009369), Diabetes (MESH:D003920), vascular disease (MESH:D014652), bacteria (MESH:C000719206), inflammation (MESH:D007249), wounds (MESH:D014947), hyperglycemia (MESH:D006943), MRSA (MESH:D013203), T1DM (MESH:D003922), Bacterial (MESH:D001424), CAM (MESH:D015433), Toxicity (MESH:D064420), Diabetic wound infections (MESH:D014946), EPS (MESH:C535509), ulcers (MESH:D014456), infected (MESH:D007239), diabetic neuropathy (MESH:D003929), immune dysfunction (MESH:D007154), diabetes complications (MESH:D048909), hyperglycemic (MESH:D006944), diabetic foot ulcers (MESH:D017719), Chronic infections (MESH:D000088562)
- **Chemicals:** Methicillin (MESH:D008712), ethanol (MESH:D000431), blood sugar (MESH:D001786), naftifine (MESH:C029178), NaOH (MESH:D012972), hydroxyl (MESH:D017665), Ce (MESH:D002563), KBr (MESH:C039004), Cu (MESH:D003300), 5,5'-dithiobis 2-(nitro benzoic acid) (MESH:D004228), DCFH-DA (MESH:C029569), isoflurane (MESH:D007530), streptozotocin (MESH:D013311), Staphyloxanthin (MESH:C031841), 2'7'-dichlorofluorescein (MESH:C037631), phenol (MESH:D019800), water (MESH:D014867), E (MESH:D004540), Zinc oxide (MESH:D015034), CeO2 (MESH:C030583), carotenoid (MESH:D002338), MB (MESH:D008751), Coomassie brilliant blue G-250 (MESH:C004692), agar (MESH:D000362), Triton-X 100 (MESH:D017830), polymer (MESH:D011108), C (MESH:D002244), 2'7'-dichlorodihydrofluorescein diacetate (MESH:C110400), streptomycin (MESH:D013307), PPY (MESH:C067635), 3,3'',5,5''-tetramethylbenzidine (MESH:C021758), xylene (MESH:D014992), polysaccharide (MESH:D011134), N (MESH:D009584), P (MESH:D010758), formazan (MESH:D005562), O (MESH:D010100), Salicylic acid (MESH:D020156), Zinc (MESH:D015032), Metal (MESH:D008670), Zinc acetate dihydrate (MESH:D019345), methionine (MESH:D008715), sodium chloride (MESH:D012965), gold (MESH:D006046), methanol (MESH:D000432), singlet oxygen (MESH:D026082), DMSO (MESH:D004121), nitric acid (MESH:D017942), glucose (MESH:D005947), creatinine (MESH:D003404), H2SO4 (MESH:C033158), ROS (MESH:D017382), oxide (MESH:D010087), glutaraldehyde (MESH:D005976), Eosin (MESH:D004801), H (MESH:D006859), lipids (MESH:D008055), urea nitrogen (MESH:C530477), paraformaldehyde (MESH:C003043), pyrrole (MESH:D011758)
- **Species:** Pseudomonas aeruginosa (species) [taxon 287], Mus musculus (house mouse, species) [taxon 10090], Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606], Staphylococcus aureus (species) [taxon 1280], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]
- **Cell lines:** NIH-3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12928003/full.md

## References

81 references — full list in the complete paper: https://tomesphere.com/paper/PMC12928003/full.md

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Source: https://tomesphere.com/paper/PMC12928003