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Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration.

ABSTRACT: Mesenchymal stem cell (MSC)-based therapies have been used in skin regeneration due to their ability to differentiate into many cells, promote cytokine secretion and participate in collagen deposition. In this study, we concluded that a CuS@BSA nanoparticles exhibited similar potential in inducing MSCs differentiation to fibroblasts as Cu ions for wound healing. Methods: First, we verified the photothermal efficiency of CuS@BSA in vivo and vitro and had no cytotoxicity for MSCs when the temperature was controlled at 42 °C by adjusting the power of irradiation at 980 nm. And then we detected the expression of vimentin in MSCs, which further directed the MSCs to fibroblasts through Western blotting and Immunofluorescence when treated with CuS@BSA or pre-heat at 42 °C. In addition, we implanted MSCs into the Matrigel or electrospun PLA nanofiber membrane in vitro to evaluating the effect of heating or CuS@BSA on the morphological change of MSCs by SEM. Finally, we evaluated improving skin regeneration by the combination of preheated-MSCs and CuS@BSA nanoparticles that were encapsulated in Matrigel. Results: The CuS@BSA nanoparticles have good photothermal conversion efficiency. Not only CuS nanoparticles itself or after irradiation at 980 nm stimulated the expressioin of vimentin in MSCs. Besides, the CuS@BSA can promote cell proliferation as Cu ion through the expression of ERK. The combination of the CuS@BSA nanoparticles and thermal treatment synergistically improved the closure of an injured wound in an injured wound model. Conclusions: MSCs combined with CuS@BSA are a promising wound dressing for the reconstruction of full-thickness skin injuries.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC6993219 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration.

Xiao Yao Y Peng Jinrong J Liu Qingya Q Chen Lijuan L Shi Kun K Han Ruxia R Yang Qian Q Zhong Lin L Zha Ruoyu R Qu Ying Y Qian Zhiyong Z

Theranostics 20200101 4

Mesenchymal stem cell (MSC)-based therapies have been used in skin regeneration due to their ability to differentiate into many cells, promote cytokine secretion and participate in collagen deposition. In this study, we concluded that a CuS@BSA nanoparticles exhibited similar potential in inducing MSCs differentiation to fibroblasts as Cu ions for wound healing. Methods: First, we verified the photothermal efficiency of CuS@BSA in vivo and vitro and had no cytotoxicity for M ...[more]

PMID: 32042318

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Project description:The objective of this study was to evaluate the in vivo application and photothermal ablation effects and mechanism of copper sulfide nanoparticles (CuS NPs) in hepatocellular carcinoma (HCC). Sheet-like CuS-BSA NPs with a particle size of 30 nm were synthesized using bovine serum albumin (BSA) as a biological modifier, and were physically characterized. To provide a reference range for the biosafety dose of CuS-BSA NPs, 36 male Kunming mice were randomly assigned into six groups. Different one-time doses of CuS-BSA NPs were injected via tail vein injection, and the potential damages of liver, kidney and spleen were observed 14 days later. To evaluate the in vivo photothermal effect of CuS-BSA NPs, 48 male Kunming mice were used to establish the H22 hepatoma-bearing mouse model and were randomly assigned into six groups. CuS-BSA NPs (600 μg/kg) were injected via tail vein or intratumoral injection. Irradiations were performed 30 min after injection, with a 980 nm near-infrared laser (2.0 W/cm2) for 10 min once a week for 3 weeks. The results indicated that the CuS-BSA NPs had good dispersibility in three different solvents and had a strong absorption peak at 980 nm. The heating curves demonstrated that the photothermal effects of CuS-BSA NPs aqueous solution exhibited concentration dependence and power density dependence. In the in vivo experiment, when the doses of CuS-BSA NPs were in the range of 1800-7,200 μg/kg, the thymus index and spleen index of mice were not significantly different from those of the control group, and the structures of liver, kidney and spleen were intact without remarkable pathological changes. A lower dose of CuS-BSA NPs (600 μg/kg) could effectively inhibit tumor growth in H22 hepatoma-bearing mice at 980 nm NIR. Moreover, under the near-infrared laser irradiation, both in the tail vein injection group and the intratumoral injection group, a large area of necrosis in the tumor tissue, as well as the up-regulation of apoptotic proteins including cleaved caspase-3 and cleaved caspase-9 were observed. CuS-BSA NPs are promising photothermal agents in the photothermal therapy of cancer.

Project description:Rationale: Chemodynamic therapy (CDT) based on the Fe(II)-mediated Fenton reaction is an emerging tumor treatment strategy. However, the catalytic efficiency in tumors is crucially limited by Fe(II). Herein, an endogenous hydrogen sulfide (H2S) accelerated Fe(III)/Fe(II) transformation and photothermal synergistically enhanced CDT strategy based on ellagic acid-Fe-bovine serum albumin (EA-Fe@BSA) nanoparticles (NPs) was developed for colon tumor inhibition. On the one hand, the Fe(III) with low catalytic activity in the EA-Fe@BSA NPs could be rapidly reduced to the highly active Fe(II) by the abundant H2S in colon cancer tissues. Thus, a rapid Fe(III)/Fe(II) conversion system was established, wherein highly active Fe(II) ions were continuously regenerated to improve the CDT efficiency. On the other hand, the photothermal effect of EA-Fe@BSA NPs also accelerated the production of hydroxyl radicals (•OH), thereby synergistically enhancing the CDT performance and improving the therapeutic efficacy. Methods: The endogenous H2S accelerated Fe(III)/Fe(II) conversion and PTT enhanced CDT were investigated by characterization of the Fe valence state and detection of •OH. T 1-weighted magnetic resonance imaging (MRI) was tested both in vitro and in vivo. The biocompatibility of NPs were examined via MTT assay, hemolysis analysis and routine blood measurements. The enhanced CDT was investigated in HCT116 colon cancer cells by Calcein-AM/PI staining and MTT assay, and tumor inhibition was demonstrated in HCT116 tumor bearing mice. Results: In this work, EA-Fe@BSA NPs were constructed as a CDT theranostic reagent. The H2S accelerated Fe(III)/Fe(II) conversion was confirmed, more degradation of MB and generation of •OH demonstrated the enhanced CDT in vitro. EA-Fe@BSA NPs exhibited good T 1-weighted MRI performance. More importantly, it displayed strong near-infrared (NIR) absorption and excellent photothermal efficiency, further promotes the production of •OH. Hence, the efficacy of CDT was enhanced, and the tumor growth was inhibited efficiently. Conclusion: All results demonstrate that this strategy based on endogenous H2S promoted Fe(III)/Fe(II) transformation together with PTT acceleration permits efficient Fenton-reaction- mediated CDT both in vitro and in vivo, which holds great potential for effective colon cancer theranostics.

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Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration.

Publications

Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration.

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