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Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health, especially among immunocompromised populations. Given the intricate problem of dramatic increase in resistance to common biocides, the development of safe and efficient biocide formulated agents to alleviate drug resistance is highly demanding. In this study, Schiff-base ligands were successfully formed on natural biopolymer of epsilon-poly-L-lysine (ε-PL) decorated aldehyde functionalized mesoporous silica SBA-15 (CHO-SBA-15) for the selective coordination of silver ions, which was affirmed by various physicochemical methods. Besides the identified broad-spectrum antibacterial activities, the as-prepared Schiff-base silver nanocomplex (CHO-SBA-15/ε-PL/Ag, CLA-1) exhibited an improved inhibitory effect on infectious pathogen growth typified by Escherichia coli and Staphylococcus aureus in comparison with two control silver complexes without Schiff-base conjugates, SBA-15/ε-PL/Ag and CHO-SBA-15/Ag, respectively. In addition, CLA-1 remarkably inhibited the growth of Mycobacterium tuberculosis due to the excellent antimicrobial activity of silver species. Significantly, CLA-1 kills Candida albicans cells, inhibits biofilm formation, and eliminates preformed biofilms, with no development of resistance during continuous serial passaging. The antifungal activity is connected to disruption of bacterial cell membranes and increased levels of intracellular reactive oxygen species. In mouse models of multidrug-resistant C. albicans infection, CLA-1 exhibited efficient in vivo fungicidal efficacy superior to two antifungal drugs, amphotericin B and fluconazole. Moreover, CLA-1 treatment induces negligible toxicity against normal tissues with safety. Therefore, this study reveals the pivotal role of the molecular design of Schiff-base silver nanocomplex formation on biopolymer surface-functionalized silica mesopores as a green and efficient nanoplatform to tackle infectious microbes.


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Schiff-base silver nanocomplexes formation on natural biopolymer coated mesoporous silica contributed to the improved curative effect on infectious microbes

Show Author's information Ling Cai1,§Yanqiang Huang2,3,§Yuanyuan Duan4,§Qiao Liu1,§Qilan Xu1Jia Jia2Jianming Wang1Qian Tong2Peipei Luo2Yujie Wen5Luming Peng5Qian Wu2Xudong Hang2Huijun Jiang6Ping Zhu1Yanmei Yang2Boshen Zhou2Liping Zeng2Hongkai Bi2,7( )Jin Chen1,8( )
Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing 211166, China
Research Center for the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, China
The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China
Key Laboratory of Mesoscopic Chemistry of MOE and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Department of Gastroenterology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China
Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China

§ Ling Cai, Yanqiang Huang, Yuanyuan Duan, and Qiao Liu contribute equally to this work.

Abstract

Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health, especially among immunocompromised populations. Given the intricate problem of dramatic increase in resistance to common biocides, the development of safe and efficient biocide formulated agents to alleviate drug resistance is highly demanding. In this study, Schiff-base ligands were successfully formed on natural biopolymer of epsilon-poly-L-lysine (ε-PL) decorated aldehyde functionalized mesoporous silica SBA-15 (CHO-SBA-15) for the selective coordination of silver ions, which was affirmed by various physicochemical methods. Besides the identified broad-spectrum antibacterial activities, the as-prepared Schiff-base silver nanocomplex (CHO-SBA-15/ε-PL/Ag, CLA-1) exhibited an improved inhibitory effect on infectious pathogen growth typified by Escherichia coli and Staphylococcus aureus in comparison with two control silver complexes without Schiff-base conjugates, SBA-15/ε-PL/Ag and CHO-SBA-15/Ag, respectively. In addition, CLA-1 remarkably inhibited the growth of Mycobacterium tuberculosis due to the excellent antimicrobial activity of silver species. Significantly, CLA-1 kills Candida albicans cells, inhibits biofilm formation, and eliminates preformed biofilms, with no development of resistance during continuous serial passaging. The antifungal activity is connected to disruption of bacterial cell membranes and increased levels of intracellular reactive oxygen species. In mouse models of multidrug-resistant C. albicans infection, CLA-1 exhibited efficient in vivo fungicidal efficacy superior to two antifungal drugs, amphotericin B and fluconazole. Moreover, CLA-1 treatment induces negligible toxicity against normal tissues with safety. Therefore, this study reveals the pivotal role of the molecular design of Schiff-base silver nanocomplex formation on biopolymer surface-functionalized silica mesopores as a green and efficient nanoplatform to tackle infectious microbes.

Keywords: drug delivery, drug resistance, mesoporous silica, antimicrobial, silver nanoparticles, biopolymer

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Received: 08 September 2020
Revised: 26 November 2020
Accepted: 02 December 2020
Published: 20 January 2021
Issue date: August 2021

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© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported by the National Key R&D Programs of China (No. 2018YFC0311003 to H. B.), the National Natural Science Foundation of China (No. U1703118 to J. C.), the Natural Science Foundation of Jiangsu Province (No. BK20181364 to J. C.), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, to J. C.), the Cooperative Project between Southeast University and Nanjing Medical University (No. 2018DN0004 to J. C.), the National Science Foundation of the Jiangsu Higher Education Institutions of China (No. 18KJA310002 to H. B., No. 19KJA310003 to J. C.), the Jiangsu Specially Appointed Professor and Jiangsu Medical Specialist Programs of China (to H. B.), and Jiangsu Province "Innovative and Entrepreneurial Team" Program.

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