Copper-incorporated Calcium Silicate Nanorods Composite Hydrogels for Tumor Therapy and Skin Wound Healing

doi:10.15541/jim20220164

Abstract

Abstract:

Developing a hydrogel with tumor therapy and skin wound healing is of great significance for eliminating residual tumor cells and promoting skin wound healing after surgical resection of skin cancers. Here, copper- incorporated calcium silicate (Cu-CS) nanorods were prepared by a molten salt method with calcium hydrate silicate as matrix, NaCl and KCl as molten salt, and CuSO₄·5H₂O as Cu source, and then incorporated into sodium alginate (SA) hydrogel to achieve Cu-CS/SA composite hydrogel. The results showed that Cu content of Cu-CS nanorods increased with the increase of the Cu source addition and the treatment temperature, but their catalytic activity for producing hydroxy radical (·OH) from H₂O₂ exhibited the trend of increasing and then decreasing. Nanorods, prepared with 3% copper source (3Cu-CS) at 700 ℃, displayed the best catalytic performance. Cu with +2 valence state could be uniformly distributed on the surface of Cu-CS nanorods, with Cu content as low as 0.61%. Importantly, Cu-CS/SA hydrogel with Cu-CS nanorods less than 20% were biocompatible and could catalyze H₂O₂ to produce cytotoxic ·OH in a simulated tumor microenvironment, exhibiting outstanding chemodynamic effect. Furthermore, Cu-CS/SA hydrogel could promote proliferation and migration of human umbilicle vein endothelial cells and human dermal fibroblast. Therefore, Cu-CS/SA hydrogel is a promising material for applying in tumor therapy and skin wound healing.

Key words: molten salt method, copper-incorporated calcium silicate nanorods, hydrogel, chemodynamic therapy, skin wound healing

CLC Number:

TQ174

WU Aijun, ZHU Min, ZHU Yufang. Copper-incorporated Calcium Silicate Nanorods Composite Hydrogels for Tumor Therapy and Skin Wound Healing[J]. Journal of Inorganic Materials, 2022, 37(11): 1203-1216.

Figures/Tables 13

Fig. 1 XRD patterns of Cu-CS powders prepared by molten salt method with (a) different amounts of copper salt and (b) different temperatures

Fig. 2 SEM images of (a) CSH, (b) CS and (c) 3Cu-CS powders

Fig. 3 (a) TEM image, (b) EDS spectrum and (c) elemental mapping of 3Cu-CS nanorods The color figure can be obtained from online edition

Fig. 4 (a) Cu2p XPS spectrum of 3Cu-CS nanorods, Cu amounts of Cu-CS nanorods prepared with (b) different copper salt additions and (c) different temperatures by ICP-AES method, respectively. *p< 0.05, **p< 0.01, ***p< 0.001 The color figures can be obtained from online edition

Fig. 5 Chemodynamic effects of Cu-CS nanorods (a, b) UV-Vis absorption spectra of TMB solutions with pH 6.0 and H2O2 (100 mmol/L) after adding Cu-CS nanorod (1 mg/mL) prepared by a molten salt method with (a) different copper salt additions and (b) different treatment temperatures for 30 min; (c) UV-Vis absorption spectra of TMB solutions after adding 3Cu-CS nanorods (1 mg/mL) into TMB solutions under pH 6.0 or pH 7.4 conditions and with or without H2O2 for 20 min The color figures can be obtained from online edition

Fig. 6 SEM images of the surfaces and cross sections for (a, d1, d2) SA, (b, e1, e2) 20%-CS/SA and (c, f1, f2) 20%-Cu-CS/SA hydrogels

Fig. 7 Release behaviors of (a) Ca, (b) Si and (c) Cu ions from SA, 20%-CS/SA and 20%-Cu-CS/SA hydrogels in Tris-HCl buffer The color figures can be obtained from online edition

Fig. 8 Chemodynamic effects of Cu-CS/SA hydrogels (a) UV-Vis absorption spectra of TMB solutions with pH 6.0 and H2O2 (100 mmmol/L) after adding Cu-CS/SA hydrogel (0.1 g/mL) with different contents of Cu-CS nanorods for 60 min; (b) UV-Vis absorption spectra changes of TMB solutions with time after adding 20%-Cu-CS/SA hydrogel (0.1 g/mL) under a condition of pH 6.0 and H2O2 (100 mmmol/L); (c) UV-Vis absorption spectra changes of TMB solutions with time after adding 20%-Cu-CS/SA hydrogel (0.1 g/mL) under a condition of pH 6.0; (d) UV-Vis absorption spectra changes of TMB solutions with time under a condition of pH 6.0 and H2O2 (100 mmmol/L); (e) Absorbance changes at 652 nm versus time for TMB solutions with 20%-Cu-CS/SA hydrogel under pH 6.0 or pH 7.4 conditions and with or without H2O2; (f) Absorbance changes at 652 nm versus time for TMB solutions with different concentrations of H2O2 at pH 6.0 after adding 20%-Cu-CS/SA hydrogel (0.1 g/mL). The color figures can be obtained from online edition

Fig. 9 Cell viabilities of HUVECs and HDFs after 24 h incubation with hydrogels incorporated with different contents of Cu-CS nanorods The color figure can be obtained from online edition ***: p< 0.001

Fig. 10 Fluorescence images of B16F10 cells after different treatments for observing intracellular ROS The color figures can be obtained from online edition

Fig. 11 Cell viability of B16F10 cells after different treatments ***: p< 0.001

Fig. 12 Cell proliferations of (a) HUVECs and (b) HDFs cultured with different hydrogels ns: p>0.05, **: p< 0.01, ***: p< 0.001; The color figures can be obtained from online edition

Fig. 13 (a, b) Cell migration images and (c, d) corresponding migration rates of (a, c) HUVECs and (b, d) HDFs after cultured with SA, 20%-CS/SA and 20%-Cu-CS/SA hydrogels for 24 h, respectively ( **: p< 0.01) The color figures can be obtained from online edition

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