Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of <i>Pseudomonas aeruginosa</i>-infected lung inflammation

作者全名："Xu, Yuhang; Liu, Qian; Wang, Bin; Li, Quan; Chen, Yue; Yang, Yao; Zhu, Zhihao; Gong, Daohui; Zhang, Chuan; Wang, Guansong; Qian, Hang"

作者地址："[Xu, Yuhang; Liu, Qian; Wang, Bin; Li, Quan; Chen, Yue; Yang, Yao; Zhu, Zhihao; Gong, Daohui; Wang, Guansong; Qian, Hang] Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China; [Liu, Qian] Chongqing Med Univ, Management Ctr, Lab Pharm & Chem, Chongqing 400016, Peoples R China; [Liu, Qian] Chongqing Med Univ, Lab Teaching & Management Ctr, Lab Tissue & Cell Biol, Chongqing 400016, Peoples R China; [Wang, Bin; Wang, Guansong; Qian, Hang] Chongqing Key Lab Precis Med & Prevent Major Resp, Chongqing 400037, Peoples R China; [Zhang, Chuan] Shanghai Jiao Tong Univ, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai Key Lab Mol Engn Chiral Drugs, 800 Dongchuan Rd, Shanghai 200240, Peoples R China"

通信作者："Wang, GS; Qian, H (通讯作者)，Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China.; Wang, GS; Qian, H (通讯作者)，Chongqing Key Lab Precis Med & Prevent Major Resp, Chongqing 400037, Peoples R China.; Zhang, C (通讯作者)，Shanghai Jiao Tong Univ, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai Key Lab Mol Engn Chiral Drugs, 800 Dongchuan Rd, Shanghai 200240, Peoples R China."

来源：BIOMATERIALS SCIENCE

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001185754200001

JCR分区：Q1

影响因子：5.8

年份：2024

卷号：　

期号：　

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文献类型：Article; Early Access

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摘要："Pseudomonas aeruginosa (PA) is one of the most common multidrug-resistant pathogens found in clinics, often manifesting as biofilms. However, due to the emergence of superbugs in hospitals and the overuse of antibiotics, the prevention and treatment of PA infections have become increasingly challenging. Utilizing DNA nanostructures for packaging and delivering antibiotics presents an intervention strategy with significant potential. Nevertheless, construction of functional DNA nanostructures with multiple functionalities and enhanced stability in physiological settings remains challenging. In this study, the authors propose a magnesium-free assembly method that utilizes tobramycin (Tob) as a mediator to assemble DNA nanostructures, allowing for the functionalization of DNA nanostructures by combining DNA and antibiotics. Additionally, our study incorporates maleimide-modified DNA into the nanostructures to act as a targeting moiety specifically directed towards the pili of PA. The targeting ability of the constructed functional DNA nanostructure significantly improves the local concentration of Tob, thereby reducing the side effects of antibiotics. Our results demonstrate the successful construction of a maleimide-decorated Tob/DNA nanotube (NTTob-Mal) for the treatment of PA-infected lung inflammation. The stability and biocompatibility of NTTob-Mal are confirmed, highlighting its potential for clinical applications. Furthermore, its specificity in recognizing and adhering to PA has been validated. In vitro experiments have shown its efficacy in inhibiting PA biofilm formation, and in a murine model, NTTob-Mal has exhibited significant therapeutic effectiveness against PA-induced pneumonia. In summary, the proposed antibiotic drug-mediated DNA nanostructure assembly approach holds promise as a novel strategy for targeted treatment of PA infections."

基金机构："National Natural Science Foundation of China [82270092, 32071379]; National Natural Science Foundation of China [CSTB2023NSCQ-ZDJ0017]; Major Natural Science Foundation of Chongqing, China [cstc2021ycjh-bgzxm0011]; Chongqing Talents and Natural Science Foundation of Chongqing [2022YQB024]; Young PhD Incubation Program of Xinqiao Hospital, Army Medical University"

基金资助正文："This work was supported by the National Natural Science Foundation of China (82270092 and 32071379), the Major Natural Science Foundation of Chongqing, China (CSTB2023NSCQ-ZDJ0017), Chongqing Talents and Natural Science Foundation of Chongqing (No. cstc2021ycjh-bgzxm0011), and the Young PhD Incubation Program of Xinqiao Hospital, Army Medical University (2022YQB024)."