TY - JOUR
T1 - Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms
AU - Zhou, Cailing
AU - Zhou, Yu
AU - Zheng, Yaqian
AU - Yu, Yue
AU - Yang, Kailing
AU - Chen, Zhiyong
AU - Chen, Xianhui
AU - Wen, Kang
AU - Chen, Yajie
AU - Bai, Silei
AU - Song, Junfeng
AU - Wu, Tong
AU - Lei, E.
AU - Wan, Muyang
AU - Cai, Qingyun
AU - Ma, Luyan
AU - Wong, Wing Leung
AU - Bai, Yugang
AU - Zhang, Chunhui
AU - Feng, Xinxin
N1 - Funding Information:
X.F. thanks Prof. Hang Xing (Hunan University), Dr. Kai Zhou (The First Affiliated Hospital of Southern University of Science and Technology), Dr. Hui Wang (Peking University People’s Hospital), and Dr. Cuiyan Tan (Fifth Affiliated Hospital of Sun Yat-sen University) for providing bacterial strains. The funding support from the National Natural Science Foundation of China (Grants 22177031 to X.F., 21877033 and 92163127 to Y.B., 82102415 to M.W., 21874038 to Q.C.), the Natural Science Foundation of Hunan Province (2021JJ30088 to Y.B., 2021JJ40055 to M.W.), the Research Grants Council of the Hong Kong Special Administrative Region, China (RGC Project No. 15300522 to W.W.), and the Fundamental Research Funds for the Central Universities (531118010738 to C. H.) are gratefully acknowledged.
Publisher Copyright:
© 2023 American Chemical Society
PY - 2023/4/26
Y1 - 2023/4/26
N2 - Bacterial biofilms are major causes of persistent and recurrent infections and implant failures. Biofilms are formable by most clinically important pathogens worldwide, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, causing recalcitrance to standard antibiotic therapy or anti-biofilm strategies due to amphiphilic impermeable extracellular polymeric substances (EPS) and the presence of resistant and persistent bacteria within the biofilm matrix. Herein, we report our design of an oligoamidine-based amphiphilic “nano-sword” with high structural compacity and rigidity. Its rigid, amphiphilic structure ensures effective penetration into EPS, and the membrane-DNA dual-targeting mechanism exerts strong bactericidal effect on the dormant bacterial persisters within biofilms. The potency of this oligoamidine is shown in two distinct modes of application: it may be used as a coating agent for polycaprolactone to fully inhibit surface biofilm growth in an implant-site mimicking micro-environment; meanwhile, it cures model mice of biofilm infections in various ex vivo and in vivo studies.
AB - Bacterial biofilms are major causes of persistent and recurrent infections and implant failures. Biofilms are formable by most clinically important pathogens worldwide, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, causing recalcitrance to standard antibiotic therapy or anti-biofilm strategies due to amphiphilic impermeable extracellular polymeric substances (EPS) and the presence of resistant and persistent bacteria within the biofilm matrix. Herein, we report our design of an oligoamidine-based amphiphilic “nano-sword” with high structural compacity and rigidity. Its rigid, amphiphilic structure ensures effective penetration into EPS, and the membrane-DNA dual-targeting mechanism exerts strong bactericidal effect on the dormant bacterial persisters within biofilms. The potency of this oligoamidine is shown in two distinct modes of application: it may be used as a coating agent for polycaprolactone to fully inhibit surface biofilm growth in an implant-site mimicking micro-environment; meanwhile, it cures model mice of biofilm infections in various ex vivo and in vivo studies.
KW - amphiphilic oligomers
KW - anti-bacterial biofilm
KW - extracellular polymeric substance
KW - persister cells
UR - http://www.scopus.com/inward/record.url?scp=85152641658&partnerID=8YFLogxK
U2 - 10.1021/acsami.3c03091
DO - 10.1021/acsami.3c03091
M3 - Journal article
AN - SCOPUS:85152641658
SN - 1944-8244
VL - 15
SP - 20458
EP - 20473
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 16
ER -