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. 2021 Nov 10;19(1):362.
doi: 10.1186/s12951-021-01106-w.

Tea polyphenol modified, photothermal responsive and ROS generative black phosphorus quantum dots as nanoplatforms for promoting MRSA infected wounds healing in diabetic rats

Shibo Xu  1 , Linna Chang  1 , Yanan Hu  1 , Xingjun Zhao  1 , Shuocheng Huang  1 , Zhenhua Chen  2 , Xiuli Ren  3 , Xifan Mei  4
Affiliations

Tea polyphenol modified, photothermal responsive and ROS generative black phosphorus quantum dots as nanoplatforms for promoting MRSA infected wounds healing in diabetic rats

Shibo Xu et al. J Nanobiotechnology. .

Erratum in

Abstract

Background: Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant.

Results: The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats.

Conclusions: The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics.

Keywords: Black phosphorus quantum dots; Diabetic deep-burn wound healing; Multifunctional nanoplatforms; Photocatalytic; Photothermal.

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Conflict of interest statement

No potential conflicts of interest were disclosed.

Figures

Scheme 1.
Scheme 1.
The schematic illustration of the synthesis of EGCG-BPQDs@H nanocomposite and the process of sterilization and stimulation of cell behaviors that can promote regenerative activities of the skin cells and actively participate in epidermal regeneration, and accelerate the healing in diabetic infected wounds
Fig. 1
Fig. 1
Characterization of BPQDs@H, EGCG@H, EGCG-BPQDs@H. A HRTEM images and B DLS size distribution of EGCG-BPQDs; the insert in A is the image of one single magnified BPQD. C FTIR spectra, D XRD, E UV–vis and F fluorescence emission (λex = 400 nm) of samples. G The temperature rises curves of four groups of samples within 5 min. H The thermal curves of BPQDs@H and EGCG-BPQDs@H after repeated laser irradiation (n = 3). I Infrared thermography images of samples under 808 nm laser irradiation for 5 min. J ABDA solution containing EGCG-BPQDs@H after irradiation for different times. K The ESR spectra of BPQDs@H and EGCG-BPQDs@H after being in the dark or irradiated with light for 10 min
Fig. 2
Fig. 2
Antimicrobial efficacy of various methods on MRSA and E. coli. A Inhibition zones and B, C the corresponding statistical graphs of MRSA and E. coli with different treatments (1: hydrogel, 2: BPQDs@H, 3: EGCG@H, 4: EGCG-BPQDs@H). D, F Digital photos of bacterial colonies on agar plates with different treatments. E, G The corresponding bacterial colonies on agar plates were calculated
Fig. 3
Fig. 3
Deformation of the external structure of bacteria disposed of by EGCG-BPQDs@H. A Calcein-AM/PI staining images of MRSA in different treatment groups. Red spots signify dead bacteria, bar = 50 μm. B The corresponding quantitative assay of live and dead bacteria. C The SEM images, bar = 500 μm
Fig. 4
Fig. 4
The investigation of antibacterial mechanisms. A Fluorescent photographs of ROS level in MRSA with various treatments in vitro, stained by DCFH-DA, bar = 100 μm. B Crystalline violet-stained biofilm. E Images of MRSA biofilms stained with crystal violet, bar = 200 μm. C Consequential statistics of histograms indicating religious ROS activity levels. D Absorbance of biofilm in different groups
Fig. 5
Fig. 5
Promoting migration and proliferation effects and potential mechanism. A Digital images of scratch wound assay in different treatments, bar = 100 μm. B Quantification of HUVEC migration. C MTT analysis in different groups. D CLSM images of the expression analysis of bFGF, bar = 25 μm. E The expression level of bFGF protein. F Quantification analysis of the bFGF protein. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 6
Fig. 6
Angiogenic tubular formation and relative protein expression of endothelial cells in vitro. A Tubular formation on Matrigel and digital analysis conversion of HUVECs in different treatments, bar = 100 μm. (B, C) Total length and the number of nodes were quantified. D CLSM images of the expression analysis of CD31, bar = 25 μm. E The expression level of CD31 and VEGF protein. F Quantification analysis of the CD31 and VEGF protein. *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 7
Fig. 7
Evaluation effects of accelerating diabetic infected burn-wound in vivo. A Images of infected burn-wound healing at different times, bar = 5 mm. B Traces of wound-bed closure during 21 days for each treatment. C Corresponding statistical graph of relative wound area from each group with different treatments. D Photothermal images of rats treated with hydrogel, BPQDs@H, EGCG@H, and EGCG-BPQDs@H with NIR irradiation at different times. E Changes in body weight of the rats
Fig. 8
Fig. 8
Evaluation on the healing-promoting effect of the nanoplatforms on infected burns rats. A H&E staining of wound sites with different treatments, the red arrow indicates intact epidermis, bar = 200 μm. B Masson staining of the wound tissues, dotted line indicates collagen at the wound, bar = 200 μm. C Western blot analysis. D Quantification for the molecules involved in the signaling pathways for burn wound healing. E Scheme diagram showing nanomaterials direct cell proliferation and enhanced fibrinogen expression to accelerate wound healing
Fig. 9
Fig. 9
Preliminary toxicity study in vivo. A Hepatorenal function test for ALT, AST, CREA and BUN. B Histological toxicological observation of H&E staining of the heart, liver, spleen, lung, and kidney with different treatments, bar = 100 μm
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