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Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection.

ABSTRACT: New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.

SUBMITTER: Qing G

PROVIDER: S-EPMC6760232 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection.

Qing Guangchao G Zhao Xianxian X Zhao Xianxian X Gong Ningqiang N Chen Jing J Li Xianlei X Gan Yaling Y Wang Yongchao Y Zhang Zhen Z Zhang Yuxuan Y Guo Weisheng W Luo Yang Y Liang Xing-Jie XJ

Nature communications 20190924 1

New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not o ...[more]

PMID: 31551496

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Project description:Chemo-photothermal therapy shows great potential for inhibiting tumor growth. However, achieving maximal chemo-photothermal synergistic efficacy is challenging because of the low efficiency of controllable chemo-drug release in response to external or internal triggers. Thus, a nano-delivery system that could effectively achieve photothermal therapy and dual stimuli-responsive (heat and pH) drug release to inhibit both primary breast tumor growth and metastases is required. Methods: Herein, a thermo- and pH-responsive polymer (mPEG-PAAV) with an upper critical solution temperature (UCST) was synthesized to fabricate a DOX- and IR780-loaded micellar system. After systematic studies of the photothermal performance and controllable drug release of mPEG-PAAV micelles/IR780+DOX under NIR irradiation at different pH values, their chemo-photothermal synergetic therapy efficacies were also estimated both in in vitro and in vivo. Results: Because of the photothermal conversion of mPEG-PAAV micelle/IR780+DOX (~200 nm, 3.82 mV), high local temperature could be induced at the tumor site under NIR laser irradiation. This hyperthermia not only produced an enhanced tumor necrosis, but also broke down the micelles under the decreased pH environment, resulting in rapid DOX release and enhanced intracellular drug accumulation after NIR laser irradiation. In addition, photoacoustic imaging (PAI) of mPEG-PAAV/IR780+DOX micelle was adopted to monitor the morphology and micro-vascular distribution of the tumor tissue, which could also guide the chemo-photothermal therapy. Most importantly, the systemic administration of mPEG-PAAV micelles/IR780+DOX combined with NIR laser irradiation could simultaneously eliminate the 4T1 breast tumor and thoroughly suppress lung metastasis without any obvious adverse effects. Conclusion: Herein, a pH- and thermo-dual responsive UCST micelle system was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and PA imaging guidance for chemo-photothermal synergistic therapy of both primary breast tumors and their metastases.

Dataset Information

Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection.

Publications

Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection.

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