Preparation and Properties of Antibacterial and Antioxidant NO Releasing Hydrogels
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摘要: 设计合成了具有光热和NO控释放性的抗菌、抗氧化水凝胶。利用Fe3+和戊二醛将聚赖氨酸、单宁酸交联形成水凝胶,并负载NO供体分子S-亚硝基-N-乙酰基-DL-青霉胺获得兼具光热和NO控释功能的水凝胶(NO-Fex-TA20, x = 5, 7, 9)。所合成水凝胶具有良好的光热性能,在1 W/cm2近红外光照射下10 min内温度可达到43.8 ℃。在可见光和37 °C恒温下,水凝胶3 h累计释放的NO达到36.48 µM。抗菌实验表明,水凝胶对金黄色葡萄球菌具有优异的杀菌活性,杀菌活性大于99.9%;同时,其能够高效清除2,2-联苯基-1-苦基胼基(DPPH)自由基,清除率大于84.3%,具有显著的抗氧化效果。Abstract: Bacterial infection seriously endangers patients' health. Thus, it is imperative to develop highly efficient antibacterial materials. In this study, antibacterial and antioxidant hydrogel with photothermal effect and nitric oxide (NO) gas-releasing property was designed and synthesized. The hydrogel was formed by crosslinking ε-polylysine and tannic acid using Fe3+ and glutaraldehyde and loading NO donor S-nitroso-N-acetyl-DL penicillamine (SNAP). The NO-Fe9-TA20 hydrogel shows high photothermal effect and the temperature of hydrogel can reach 43.8 ℃ within 10 minutes under 1 W/cm2 near-infrared irradiation. Additionally, the NO-Fe9-TA20 hydrogel shows effective NO-release activities. Under visible light and at 37 ℃, the amount of NO released from the hydrogel reached 36.48 μM within 3 h. Benefitting from the synergetic effect of cations of ε-poly-L-lysine (EPL) and the released NO, NO-Fe9-TA20 hydrogel exhibits antibacterial activity (> 99.9%) towards Staphylococcus aureus, and can effectively scavenge 1,1-dipheny-2-picrylhydrazyl (DPPH) free radicals (> 84.3%), which may protect cells from oxidative stress damage. This study may provide a new approach for bacterial infections treatment.
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Key words:
- antibacterial /
- antioxidant /
- nitric oxide /
- ε-polylysine /
- hydrogel
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图 3 (a) Fex-TA20水凝胶在NIR光照射下的温度曲线; (b) Fe9-TA20水凝胶在不同功率 NIR 照射下的温度曲线; (c) Fe9-TA20水凝胶的加热-冷却曲线; (d) NIR照射Fe9-TA20水凝胶的热红外图
Figure 3. (a) Temperature curves of Fex-TA20 hydrogels under NIR irradiation; (b) Temperature curves of Fe9-TA20 hydrogel under NIR irradiation with different irradiation power; (c) Heating-cooling curve of Fe9-TA20 hydrogel; (d) Thermal infrared images of Fe9-TA20 hydrogel irradiated by NIR
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[1] 郭伟, 张杰, 李颖. 细菌的致病性 [J]. 中国医疗前沿,2008(4):8-9. doi: 10.3969/j.issn.1673-5552.2008.04.005GUO W, ZHANG J, LI Y. Pathogenicity of bacteria [J]. China Healthcare Innovation,2008(4):8-9. doi: 10.3969/j.issn.1673-5552.2008.04.005 [2] PRISTOVSEK P, KIDRIC J. The search for molecular determinants of LPS inhibition by proteins and peptides [J]. Current Topics,2004,4(11):1185-1201. [3] 郭尚春, 赵丽萍, 陶诗聪, 张长青. 胞外囊泡在细菌致病机制中作用的研究进展 [J]. 中国修复重建外科杂志,2018,32(12):1597-1604. doi: 10.7507/1002-1892.201805075GUO S C, ZHAO L P, TAO S C, ZHANG C Q. Research progress on the role of extracellular vesicles in bacterial pathogenesis [J]. Chinese Journal of Reparative and Reconstructive Surgery,2018,32(12):1597-1604. doi: 10.7507/1002-1892.201805075 [4] SHARIFI S, HAJIPOUR M J, GOULD L, MORTEZA M. Nanomedicine in healing chronic wounds: opportunities and challenges [J]. Molecular Pharmaceutics,2021,18(2):550-575. doi: 10.1021/acs.molpharmaceut.0c00346 [5] SUN B K, SIPRASHVILI Z, KHAVARI P A. Advances in skin grafting and treatment of cutaneous wounds [J]. Science,2014,346(6212):941-945. doi: 10.1126/science.1253836 [6] ZENG Q K, QI X L, SHI G Y, ZHANG M, HACICK H. Wound dressing: From nanomaterials to diagnostic dressings and healing evaluations [J]. ACS Nano,2022,16(2):1708-1733. doi: 10.1021/acsnano.1c08411 [7] HICKMAN D A, PAWLOWSKI C L, SEKHON U D S, MARKS J, GUPTA A S. Biomaterials and advanced technologies for hemostatic management of bleeding [J]. Advanced Materials,2017,30(4):1700859. [8] LIANG Y P, HE J H, GUO B. Functional hydrogels as wound dressing to enhance wound healing [J]. ACS Nano,2021,15(8):12687-12722. doi: 10.1021/acsnano.1c04206 [9] ANDRÉN O C J, INGVERUD T, HULT D, HAKANSSON J, BOGESRAL Y, CAOUS J S, BLOM K, ZHANG Y N, ANDERSSON T, PEDERSEN E, BJORN C, LOWENHIELM P, MALKOCH M. Antibiotic‐free cationic dendritic hydrogels as surgical‐site‐infection‐inhibiting coatings[J], Advanced Healthcare Materials, 2019, 8: 1801619. [10] DU C S, GAO D, GAO M S, YUAN H B, LIU X N, WANG B, XING C F. Property regulation of conjugated oligoelectrolytes with polyisocyanide to achieve efficient photodynamic antibacterial biomimetic hydrogels [J]. ACS Applied Materials & Interfaces,2021,13(24):27955-2762. [11] YU L D, HU P, CHEN Y. Gas-generating nanoplatforms: Material chemistry, multifunctionality and gas therapy [J]. Advanced Materials,2018,30:18019. [12] AKHTAR M J, AHAMED M, ALHADLAQ H, ALROKAYAN S. Pt-coated Au nanoparticle toxicity is preferentially triggered via mitochondrial nitric oxide/reactive oxygen species in human liver cancer (HepG2) cells [J]. ACS Omega,2021,6(23):15431-15441. doi: 10.1021/acsomega.1c01882 [13] KANG M L, KIM H S, YOU J. Hydrogel cross-linking programmed release of nitric oxide regulates source-dependent angiogenic behaviors of human mesenchymal stem cell[J]. Science Advances, 2020, 6(9): eaay5413. [14] SUN Y J, WEN R L, YU D, ZHU Y W, ZHENG L, LIU X D, WANG H R, YU B R, XU F J. Flexible electrostatic hydrogels from marine organism for nitric oxide-enhanced photodynamic therapy against multidrug-resistant bacterial infection [J]. Science China Materials,2022,65:2850-2860. doi: 10.1007/s40843-022-2024-6 [15] ZHOU Y, TAN J Y, DAI Y P, YU Y M, ZHANG Q, MEYERHOFF M E. Synthesis and nitric oxide releasing properties of novel fluoro S-nitrosothiols [J]. Chemical Communications,2019,55(3):401-404. doi: 10.1039/C8CC08868C [16] DOU J, YANG R, JIN X X, LI P F, HAN X, WANG L J, CHI B, SHEN J, YUAN J. Nitric oxide-releasing polyurethane/S-nitrosated keratin mats for accelerating wound healing [J]. Regenerative Biomaterials,2022,9:rbac006. doi: 10.1093/rb/rbac006 [17] MONDAL A, DOUGLASS M, HOPKINS S P, SINGHA P, TRAN M, HANDA H, BRISBOIS E J. Multifunctional S-nitroso-N-acetyl-penicillamine-incorporated medical-grade polymer with selenium interface for biomedical applications [J]. ACS Applied Materials & Interfaces,2019,11(38):34652-34662. [18] 袁颖慧. 离子液体基抗菌涂层的设计合成与性能研究[D]. 上海: 东华大学, 2022.YUAN Y H. Design, synthesis and performance study of ionic liquid-based antimicrobial coatings[D]. ShangHai: DongHua University, 2022. [19] GUO S, YAO M H, ZHANG D, HE Y M, CHANG R, REN Y K, GUAN F X. One-step synthesis of multifunctional chitosan hydrogel for full-thickness wound closure and healing [J]. Advanced Healthcare Materials,2022,11(4):e2101808. doi: 10.1002/adhm.202101808 [20] ROPER D K, AHN W, HOEPFNER M. Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles [J]. The Journal of Physical Chemistry C,2007,111(9):3636-3641. doi: 10.1021/jp064341w [21] KIM Y E, KIM J. ROS-scavenging therapeutic hydrogels for modulation of the inflammatory response[J]. ACS Applied Materials & Interfaces, 2022, 14(20): 23002–23021. [22] YU M, TANG P F, TANG Y H, WEI C, WANG Z M, ZHANG H P. Breathable, moisturizing, anti-oxidation SSD-PG-PVA/KGM fibrous membranes for accelerating diabetic wound tissue regeneration [J]. ACS Applied Bio Materials,2022,5(6):2894-2901. doi: 10.1021/acsabm.2c00255 [23] GÜLçIN I, HUYUT Z, ELMASTAS M, ABOUL-ENEIN H Y. Radical scavenging and antioxidant activity of tannic acid [J]. Arabian Journal of Chemistry,2010,3(1):43-53. doi: 10.1016/j.arabjc.2009.12.008 [24] PUCCI C, MARTINELLI C, PASQUALE D D, BATTAGLIMI M, LEO N D, DEGL’INNOCENTI A, GÜMÜş M B, DRAGO F, CIOFANI G. Tannic acid-iron complex-based nanoparticles as a novel tool against oxidative stress [J]. ACS Applied Materials & Interfaces,2022,14(14):15927-15941. [25] KANG M L, KIM H S, YOU J, CHOL Y S, KWON B J, PARK C H, BAEK W, KIM M S, LEE Y J, IM G I, YOON J K, LEE J B, SUNG H J. Hydrogel cross-linking programmed release of nitric oxide regulates source-dependent angiogenic behaviors of human mesenchymal stem cell [J]. Science Advances,2020,6(9):aay5413. doi: 10.1126/sciadv.aay5413 [26] KIM C, DIRING S, FURUKAWA S, KITAGAWA S. Light-induced nitric oxide release from physiologically stable porous coordination polymers [J]. Dalton Transactions,2015,44(34):15324-15333. doi: 10.1039/C5DT01418B [27] SEYFI R, KAHAKI F A, EBRAHIMI T, MONTAZERSAHEB S, EYVAZI S, BABAEIPOUR V, TARHRIZ V. Antimicrobial peptides (AMPs): Roles, functions and mechanism of action [J]. International Journal of Peptide Research and Therapeutics,2020,26:1451-1463. doi: 10.1007/s10989-019-09946-9 [28] TAN P, FU H Y, MA X. Design, optimization, and nanotechnology of antimicrobial peptides: From exploration to applications [J]. Nano Today,2021,39:101229. doi: 10.1016/j.nantod.2021.101229 [29] 朱欣怡, 丁圣刚, 聂旋, 尤业字. 抗菌阳离子聚合物的研究进展[J]. 功能高分子学报, 2023, 36(3):ZHU X Y, DING S G, NIE X, YOU Y Z. Progress of antibacterial polycation[J]. Journal of Functional Polymers, 2023, 36(3): [30] YE R S, XU H Y, WAN C X, PENG S S, WANG L J, XU H, AGUILAR Z P, XIONG Y H, ZENG Z L, WEI H. Antibacterial activity and mechanism of action of ε-poly-L-lysine [J]. Biochemical and Biophysical Research Communications,2013,439(1):148-153. doi: 10.1016/j.bbrc.2013.08.001 [31] YU S M, LI G W, LIU R, MA D, XUE W. Dendritic Fe3O4@poly(dopamine)@PAMAM nanocomposite as controllable NO-releasing material: A synergistic photothermal and NO antibacterial study [J]. Advanced Functional Materials,2018,28(20):1707440. doi: 10.1002/adfm.201707440 -