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ACS Nano, Feb 02 2025, | https://doi.org/10.1021/acsnano.4c06501 Siderophore-Functionalized Nanodrug for Treating Antibiotic-Resistant Bacteria

Siyoung Ha ^1,2, Jinyeong Kim ³, Hwi Won Seo ^1,4, Lina Kim ¹, Yoon-Sun Yi ⁵, Sung Eun Seo ⁶, Kyung Ho Kim ⁶, Soomin Kim ¹, Jai Eun An ⁶, Gyeong-Ji Kim ⁶, Kyong-Cheol Ko ³, Sangmi Jun ⁵, Choong-Min Ryu ^1,7, Oh Seok Kwon^6,8,9
¹Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
²School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, Maryland 21853, United States.
³Korea Preclinical Evaluation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
⁴Functional Genomics Program, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
⁵Korea Basic Science Institute (KBSI), Center for Bio-imaging and Translational Research, Cheongju-si 28119, Republic of Korea.
⁶SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Korea.
⁷Department of Biosystems and Bioengineering Program, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
⁸Department of Nano Science and Technology, Sungkyunkwan University, Suwon 16419, Korea.
⁹Department of Nano Engineering, Sungkyunkwan University, Suwon 16419, Korea.

S.H., J.K., and H.W.S. contributed equally to this work.
Corresponding Authors : Choong-Min Ryu, Oh Seok Kwon

Abstract

The development of nanodrugs targeting multidrug-resistant bacteria, while sparing the beneficial constituents of the microbiome, has emerged as a promising approach to combat disease and curb the rise of antimicrobial resistance. In this investigation, we devised a siderophore-functionalized nanodrug based on a gold nanoparticle construct (AuNP-NSC; Gold nanoparticle_N-heterocyclic_Siderophore_Cyanine7), offering an innovative treatment modality against drug-resistant bacterial pathogens. As a proof of concept, the efficacy of this nanodrug delivery and antimicrobial therapy was evaluated against the notoriously resistant bacterium P. aeruginosa. N-Heterocyclic carbenes (NHCs) exhibit a strong affinity for transition metals, forming highly stable complexes resistant to ligand displacement. The entry of siderophore-conjugated nanodrugs into bacteria is facilitated through specific receptors on the outer membrane. In our study, AuNP-NSC was specifically targeted and imported into resistant Gram-negative P. aeruginosa via binding with ferric iron. Treatment with the developed nanodrug significantly inhibited the proliferation of antibiotic-resistant P. aeruginosa, reducing bacterial counts by more than 95% and mitigating drug resistance. Furthermore, AuNP-NSC markedly diminished P. aeruginosa-induced skin lesions and forestalled systemic organ failure triggered by secondary sepsis in mouse models. These findings underscore the potential of nanodrugs as specialized therapeutic agents for the management of antibiotic-resistant bacterial infections.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-03)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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