Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis
Abstract Bacterial biofilms are one of the major contributors to the refractoriness of septic arthritis. Although nitric oxide (NO)-enhanced photodynamic (PDT) therapy has been involved in biofilm eradication, the anti-biofilm efficacy is usually hindered by the short half-life and limited diffusion...
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BMC
2024-11-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-02953-z |
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| author | Shixin Liu Yuanfang Jiang Yu Zhang Kai Lv Jiaxin Zhu Mei Liu Hao Xu Genlong Jiao Wanyong Yang Guodong Sun Dong Ma |
| author_facet | Shixin Liu Yuanfang Jiang Yu Zhang Kai Lv Jiaxin Zhu Mei Liu Hao Xu Genlong Jiao Wanyong Yang Guodong Sun Dong Ma |
| author_sort | Shixin Liu |
| collection | DOAJ |
| description | Abstract Bacterial biofilms are one of the major contributors to the refractoriness of septic arthritis. Although nitric oxide (NO)-enhanced photodynamic (PDT) therapy has been involved in biofilm eradication, the anti-biofilm efficacy is usually hindered by the short half-life and limited diffusion distance of active molecules. Herein, we report a three-arm structure using the photosensitive core chlorin e6 to integrate three α-cyclodextrin (α-CD) polyrotaxane chains as the supramolecular nanocarrier of NO-enhanced PDT therapy, in which NO was loaded on the cationic rings (α-CDs). Beneficial from the enhanced permeability of the nanocarrier due to the collective act on biofilms by the molecular motions (slide and rotation of rings) of three chains in different directions, NO capable of inducing biofilm dispersal and reactive oxygen species were efficiently delivered deep inside biofilms under 660 nm laser irradiation, and reactive nitrogen species with stronger bactericidal ability was produced in-situ, further accomplishing bacteria elimination inside biofilms. In-vivo therapeutic performance of this platform was demonstrated in a rat septic arthritis model by eliminating the methicillin-resistant Staphylococcus aureus infection, and potentiating the immune microenvironment regulation and bone loss inhibition, also providing a promising strategy to numerous obstinate clinical infections caused by biofilms. Graphical Abstract |
| format | Article |
| id | doaj-art-071bc2a8912a493c8ccaf7ecf3e3be8a |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Journal of Nanobiotechnology |
| spelling | doaj-art-071bc2a8912a493c8ccaf7ecf3e3be8a2025-08-20T02:22:16ZengBMCJournal of Nanobiotechnology1477-31552024-11-0122112110.1186/s12951-024-02953-zThree-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritisShixin Liu0Yuanfang Jiang1Yu Zhang2Kai Lv3Jiaxin Zhu4Mei Liu5Hao Xu6Genlong Jiao7Wanyong Yang8Guodong Sun9Dong Ma10Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People’s Hospital), Jinan UniversityDepartment of Nuclear Medicine, PET/CT-MRI Center, The First Affiliated Hospital of Jinan UniversityDepartment of Ultrasound Medicine, Zhucheng People’s HospitalKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan UniversityKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan UniversityKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan UniversityDepartment of Nuclear Medicine, PET/CT-MRI Center, The First Affiliated Hospital of Jinan UniversityDongguan Key Laboratory of Central Nervous System Injury and Repair / Department of Orthopedic Surgery, The Sixth Affiliated Hospital of Jinan University (Dongguan)The Fifth Affiliated Hospital, Jinan UniversityGuangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People’s Hospital), Jinan UniversityGuangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People’s Hospital), Jinan UniversityAbstract Bacterial biofilms are one of the major contributors to the refractoriness of septic arthritis. Although nitric oxide (NO)-enhanced photodynamic (PDT) therapy has been involved in biofilm eradication, the anti-biofilm efficacy is usually hindered by the short half-life and limited diffusion distance of active molecules. Herein, we report a three-arm structure using the photosensitive core chlorin e6 to integrate three α-cyclodextrin (α-CD) polyrotaxane chains as the supramolecular nanocarrier of NO-enhanced PDT therapy, in which NO was loaded on the cationic rings (α-CDs). Beneficial from the enhanced permeability of the nanocarrier due to the collective act on biofilms by the molecular motions (slide and rotation of rings) of three chains in different directions, NO capable of inducing biofilm dispersal and reactive oxygen species were efficiently delivered deep inside biofilms under 660 nm laser irradiation, and reactive nitrogen species with stronger bactericidal ability was produced in-situ, further accomplishing bacteria elimination inside biofilms. In-vivo therapeutic performance of this platform was demonstrated in a rat septic arthritis model by eliminating the methicillin-resistant Staphylococcus aureus infection, and potentiating the immune microenvironment regulation and bone loss inhibition, also providing a promising strategy to numerous obstinate clinical infections caused by biofilms. Graphical Abstracthttps://doi.org/10.1186/s12951-024-02953-zPolyrotaxanesMultidirectional molecular motionsNO-enhanced PDTAnti-biofilm therapySeptic arthritis |
| spellingShingle | Shixin Liu Yuanfang Jiang Yu Zhang Kai Lv Jiaxin Zhu Mei Liu Hao Xu Genlong Jiao Wanyong Yang Guodong Sun Dong Ma Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis Journal of Nanobiotechnology Polyrotaxanes Multidirectional molecular motions NO-enhanced PDT Anti-biofilm therapy Septic arthritis |
| title | Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis |
| title_full | Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis |
| title_fullStr | Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis |
| title_full_unstemmed | Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis |
| title_short | Three-arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide-enhanced photodynamic therapy against bacterial biofilms in septic arthritis |
| title_sort | three arm polyrotaxanes with multidirectional molecular motions as the nanocarrier for nitric oxide enhanced photodynamic therapy against bacterial biofilms in septic arthritis |
| topic | Polyrotaxanes Multidirectional molecular motions NO-enhanced PDT Anti-biofilm therapy Septic arthritis |
| url | https://doi.org/10.1186/s12951-024-02953-z |
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