9-羧基fascaplysin递送系统构建及抑制胞内细菌感染初步研究
PDF下载 (96)李咏梅,裘弘达,赵 星,梁洪泽.9-羧基fascaplysin递送系统构建及抑制胞内细菌感染初步研究[J].宁波大学学报(理工版),2024,37(5):88-93.DOI:10.20098/j.cnki.1001-5132.2023.1014
LI Yongmei,QIU Hongda,ZHAO Xing,LIANG Hongze.Construction of 9-carboxylfascaplysin delivery system and preliminary inhibitory results against intracellular bacterial infection[J].Journal of Ningbo University(Natural Science & Engineering Edition),2024,37(5):88-93.DOI:10.20098/j.cnki.1001-5132.2023.1014
| Title: | Construction of 9-carboxylfascaplysin delivery system and preliminary inhibitory results against intracellular bacterial infection |
| 作者: | 李咏梅, 裘弘达, 赵 星, 梁洪泽 |
| Author(s): | LI Yongmei, QIU Hongda, ZHAO Xing, LIANG Hongze |
| 关键词: | 海洋生物碱; 胞内细菌感染; pH响应; 药物递送 |
| Keywords: | marine alkaloid; intracellular bacterial infection; pH-responsive; drug delivery |
| 分类号: | TQ463 |
| DOI: | 10.20098/j.cnki.1001-5132.2023.1014 |
| 文献标识码: | A |
| 摘要: | 针对病原体细菌引起的长期和难治愈的胞内感染难题, 以ZIF-8为载体, 9-羧基fascaplysin为抗菌活性试剂, 构建了药物递送体系. 用X射线光谱、扫描电镜、紫外-可见光谱、热重和傅里叶红外光谱对制备的材料进行了表征. 该系统具有高热稳定性, 并保持与ZIF-8一样的晶体微结构. 该体系在感染的酸性微环境中表现出pH响应性, 并可控地释放药物. 初步研究结果表明, 在胞内耐甲氧西林金黄色葡萄球菌(MRSA)感染模型中, 药物递送系统显示出以浓度依赖方式抑制胞内细菌感染的活性; 而在相同条件下, 游离9-羧基fascaplysin无法抑制胞内细菌感染. 以ZIF-8为载体的pH响应性药物递送系统是具有潜力的治疗胞内细菌感染的材料 |
| Abstract: | The current study was designed to determine the chronic and refractory intracellular infections caused by pathogenic bacteria. The drug delivery system consisting of ZIF-8 (zeolitic imidazolate framework) as a carrier and 9-carboxylfascaplysin as an antibacterial reagent was applied. The prepared material was characterized by XRD, SEM, UV-vis, TGA and FTIR. The delivery system produced higher thermal stability and remained a similar crystalline microstructure as ZIF-8. This delivery system exhibited a pH-responsive property and releases the drug in a controllable fashion under the acidic microenvironment. The preliminary data indicate that the drug delivery system showed the activity against the intracellular infection in a dose-dependent manner and the MRSA (methicillin-resistant Staphylococcus aureus) infection model. Free 9-carboxylfaspcalysin was unable to inhibit the intracellular infection under the same condition. Our results demonstrate that the ZIF-based drug delivery system with pH-responsive feature shows promising potential against the intracellular bacterial infection. |
| 参考文献 /References: | [1].LIVERMORE D M. Antibiotic resistance in staphylococci [J]. International Journal of Antimicrobial Agents, 2000, 16(Suppl.1):3-10. [2].LEVY S B, MARSHALL B. Antibacterial resistance worldwide: causes, challenges and responses[J]. Nature Medicine, 2004, 10:S122-S129. [3].VARELA M F, STEPHEN J, LEKSHMI M, et al. Bacterial resistance to antimicrobial agents[J]. Antibiotics, 2021, 10(5):593. [4].FENG W L, LI G F, KANG X X, et al. Cascade-targeting poly(amino acid) nanoparticles eliminate intracellular bacteria via on-site antibiotic delivery[J]. Advanced Materials, 2022, 34(12):e2109789. [5].ABED N, COUVREUR P. Nanocarriers for antibiotics: a promising solution to treat intracellular bacterial infections[J]. International Journal of Antimicrobial Agents, 2014, 43(6):485-496. [6].LEHAR S M, PILLOW T, XU M, et al. Novel antibody- antibiotic conjugate eliminates intracellular S. aureus[J]. Nature, 2015, 527:323-328. [7].SUBRAMANIAM S, JOYCE P, THOMAS N, et al. Bioinspired drug delivery strategies for repurposing conventional antibiotics against intracellular infections[J]. Advanced Drug Delivery Reviews, 2021, 177:113948. [8].NGUYEN L, PIETERS J. The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages[J]. Trends in Cell Biology, 2005, 15(5):269-276. [9].WANG C, YANG Y, CAO Y Y, et al. Nanocarriers for the delivery of antibiotics into cells against intracellular bacterial infection[J]. Biomaterials Science, 2023, 11(2): 432-444. [10].PETIT T J P, LEBRETON A. Adaptations of intracellular bacteria to vacuolar or cytosolic niches[J]. Trends in Microbiology, 2022, 30(8):736-748. [11].FENG W L, CHITTÒ M, MORIARTY T F, et al. Targeted drug delivery systems for eliminating intracellular bacteria[J]. Macromolecular Bioscience, 2023, 23(1):e2200311. [12].DING H T, TAN P, FU S Q, et al. Preparation and application of pH-responsive drug delivery systems[J]. Journal of Controlled Release, 2022, 348:206-238. [13].YANG Y, REIPA V, LIU G, et al. pH-sensitive compounds for selective inhibition of acid-producing bacteria[J]. ACS Applied Materials & Interfaces, 2018, 10(10):8566-8573. [14].CHEN G S, KOU X X, HUANG S M, et al. Modulating the biofunctionality of metal-organic-framework- encapsulated enzymes through controllable embedding patterns[J]. Angewandte Chemie International Edition, 2020, 59(7):2867-2874. [15].ZHANG H Y, JIANG W, LIU R L, et al. Rational design of metal organic framework nanocarrier-based codelivery system of doxorubicin hydrochloride/verapamil hydrochloride for overcoming multidrug resistance with efficient targeted cancer therapy[J]. ACS Applied Materials & Interfaces, 2017, 9(23):19687-19697. [16].REN H, ZHANG L Y, AN J P, et al. Polyacrylic acid@ zeolitic imidazolate framework-8 nanoparticles with ultrahigh drug loading capability for pH-sensitive drug release[J]. Chemical Communications, 2014, 50(8):1000- 1002. [17].李亚红, 王剑, 罗锋. ZIF-8递送生物大分子的研究进展[J]. 中国材料进展, 2022, 41(6):458-465. [18].SUN C Y, QIN C, WANG X L, et al. Zeolitic imidazolate framework-8 as efficient pH-sensitive drug delivery vehicle[J]. Dalton Transactions, 2012, 41(23):6906-6909. [19].ZHANG X, LIU L Z, HUANG L J, et al. The highly efficient elimination of intracellular bacteria via a metal organic framework (MOF)-based three-in-one delivery system[J]. Nanoscale, 2019, 11(19):9468-9477. [20].SONI R, MULLER L, FURET P, et al. Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product[J]. Biochemical and Biophysical Research Communications, 2000, 275(3):877-884. [21].ZHIDKOV M E, KAUNE M, KANTEMIROV A V, et al. Study of structure-activity relationships of the marine alkaloid fascaplysin and its derivatives as potent anticancer agents[J]. Marine Drugs, 2022, 20(3):185. [22].CHHETRI B K, TEDBURY P R, SWEENEY-JONES A M, et al. Marine natural products as leads against SARS- CoV-2 infection[J]. Journal of Natural Products, 2022, 85(3):657-665. [23].WANG X, QIU H D, YANG N, et al. Fascaplysin derivatives binding to DNA via unique cationic five-ring coplanar backbone showed potent antimicrobial/antibiofilm activity against MRSA in vitro and in vivo[J]. European Journal of Medicinal Chemistry, 2022, 230:114099. [24].QIU H D, ZHAO X, JIANG Y L, et al. Design and synthesis of fascaplysin derivatives as inhibitors of FtsZ with potent antibacterial activity and mechanistic study[J]. European Journal of Medicinal Chemistry, 2023, 254: 115348. [25].QIU H D, LIANG W D, ZHANG G J, et al. Aerobic oxidation of methyl-substituted β-carbolines catalyzed by N-hydroxyphthalimide and metal catalyst[J]. Chemistry Select, 2018, 3(43):12363-12366. [26].PAN H B, QIU H D, ZHANG K, et al. Fascaplysin derivatives are potent multitarget agents against Alzheimer’s disease: in vitro and in vivo evidence[J]. ACS Chemical Neuroscience, 2019, 10(11):4741-4756. [27].NABIPOUR H, SADR M H, BARDAJEE G R. Synthesis and characterization of nanoscale zeolitic imidazolate frameworks with ciprofloxacin and their applications as antimicrobial agents[J]. New Journal of Chemistry, 2017, 41(15):7364-7370. [28].SOLTANI B, NABIPOUR H, NASAB N A. Efficient storage of gentamicin in nanoscale zeolitic imidazolate framework-8 nanocarrier for pH-responsive drug release [J]. Journal of Inorganic and Organometallic Polymers and Materials, 2018, 28(3):1090-1097. [29].LUO D, WANG C J, TONG Y, et al. An NIF-doped ZIF-8 hybrid membrane for continuous antimicrobial treatment [J]. RSC Advances, 2020, 10(13):7360-7367. [30].HE M, YAO J F, LIU Q, et al. Facile synthesis of zeolitic imidazolate framework-8 from a concentrated aqueous solution[J]. Microporous and Mesoporous Materials, 2014, 184:55-60. [31].ZHUANG J, KUO C H, CHOU L Y, et al. Optimized metal-organic-framework nanospheres for drug delivery: evaluation of small-molecule encapsulation[J]. ACS Nano, 2014, 8(3):2812-2819. |
| 备注/Memo: | 收稿日期: 2023−10−12. 宁波大学学报（理工版）网址: http://journallg.nbu.edu.cn/ 基金项目: 宁波市“科技创新2025”重大专项（2020Z093）. 第一作者: 李咏梅, 主管护师, 主要研究方向: 药物分子. E-mail: liyongmei1@nbu.edu.cn *通信作者: 梁洪泽, 研究员, 主要研究方向: 药物分子及功能材料. E-mail: lianghongze@nbu.edu.cn 宁波大学学报（理工版）网址：http://journallg.nbu.edu.cn/ |
