β-Lactamase-Responsive Probe for Efficient Photodynamic Therapy of Drug-Resistant Bacterial Infection

Xu, Yue; Chen, Haiyan; Xu, Shiwen; Chen, Yang; Gui, Lijuan; Li, Hua; Li, Ruixi; Yuan, Zhenwei; Li, Bowen

doi:10.1021/acssensors.1c02485

Cited by 10 publications

(3 citation statements)

References 44 publications

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“…In addition to the measurements of ROS and NO production in the extracellular environment reported above, we also measured ROS and NO production in the MDR Ab , Kp and Pa bacterial cells via in situ imaging. DCFH-DA can be cleaved intracellularly and subsequently react with ROS to produce bright green fluorescent 2′,7′-dichlorodihydrofluorescein [ 63 ], which was utilized to detect ROS. As shown in Figure 4a, c and Supplementary Figure S2 , strong green DCFH-DA fluorescence was observed in IRNB-treated MDR Ab , Kp and Pa groups following irradiation with an NIR laser, suggesting that the IRNB group shows NIR laser-responsive ROS generation.…”

Section: Resultsmentioning

confidence: 99%

A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

Zhou,

Dong,

Zhao

et al. 2023

Burns &Amp; Trauma

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Background Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N′-di-sec-butyl-N, N′- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. Methods The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo. Results Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO−, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO− could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both in vitro and in vivo. Conclusions The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

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Section: Resultsmentioning

confidence: 99%

A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

Zhou,

Dong,

Zhao

et al. 2023

Burns &Amp; Trauma

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“…[168] Furthermore, other unconventional classes of photosensitizers have also emerged in APDT and being employed in treating skin and wound infections. These classes include organic dyes [61,166,[172][173][174] and aggregated-induced emission luminogens. [73,[175][176][177][178] As shown in Figure 4C, Li and his coworkers developed a bacterial metabolic labeling photosensitizer that achieve a synergistic photothermal/photodynamic effect with good biocompatibility.…”

Section: Chronic Wound Infections and Skin Infectionsmentioning

confidence: 99%

Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria

Xin

Kwek

et al. 2023

ChemPlusChem

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The emergence of multi‐drug resistant bacteria strains has been an uphill battle in modern healthcare worldwide, due to the increasing difficulty of killing them. The evolving pathogenicity of bacteria has led to researchers searching for more effective antimicrobial therapeutics to successfully eliminate them without undesirable consequences to the human body. In recent years, antimicrobial photodynamic therapy (APDT), an obsolete technique for cancer treatments, has been reported to eradicate bacteria and biofilm‐related infections. The principle of antimicrobial photodynamic therapy solely relies on the photosensitizers (PSs) generating reactive oxygen species, in the presence of oxygen and light, to destroy pathogens. Thus, it can target a broad spectrum of microorganisms, owing to the indirect interaction between PSs and the bacteria, resulting in the less likelihood for the development of drug resistant bacteria strains. This review will focus on the recent progress of APDT in the last five years and some future perspectives of APDT. The mechanism of APDT against bacteria and biofilms, various PSs used for APDT, and some common multidrug‐resistant bacteria strains will be briefly introduced. The reported in vivo applications of APDT in the several types of bacterial infections that includes periodontitis, wound infections, keratitis, endophthalmitis and tuberculosis in the last five years will be summarized in detail.

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“…coli), and vancomycin-resistant S. aureus (VRSA), and so on are represented by β -lactamase production. − The antibacterial approach using reactive oxygen species (ROS) is different from carbapenem antibiotics and is not limited by traditional resistance mechanisms, so it can inhibit the growth of drug-resistant microorganisms. − Moreover, the sterilization mechanism of ROS is derived from its oxidative properties, and this effect is not easy to induce mutation to generate new drug-resistant bacteria. − …”

Section: Introductionmentioning

confidence: 99%

Molecular Dipole Modulation of Porphyrins to Enhance Photocatalytic Oxidation Activity for Inactivation of Intracellular Bacteria

et al. 2023

ACS Biomater. Sci. Eng.

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The regulation of molecular structures of porphyrin-based photosensitizers is crucial for yielding the effective singlet oxygen as one of the efficient photocatalytic reactive oxidation species. Here, we select methoxy substitution as an electron donor to decorate the porphyrin rings. Introducing a series of metal ions into porphyrin centers further prepares the methoxysubstituted metalloporphyrins (MPs, M = Co, Ni, Cu, Zn), with the hope of modulating their molecular dipole moments and photocatalytic activity. The theoretical calculation analyses show that the metal-free porphyrin center possesses a higher transition dipole and more delocalized orbitals, leading to efficient charge transfer and improved photocatalytic activity. The metalloporphyrin samples are then polymerized by poly(D, L-lactide-co-glycolide) to be applied to in vitro sterilization experiments. As expected, metal-free porphyrin has good antibacterial ability and good biocompatibility. Moreover, the highly effective bacteriostatic metal-free porphyrin achieves satisfactory photodynamic therapeutic outcomes against intracellular pathogens in cancer cells. This work demonstrates that the molecular dipole modulation of porphyrins is critical for their photocatalytic oxidation and antibacterial ability.

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β-Lactamase-Responsive Probe for Efficient Photodynamic Therapy of Drug-Resistant Bacterial Infection

Cited by 10 publications

References 44 publications

A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria

Molecular Dipole Modulation of Porphyrins to Enhance Photocatalytic Oxidation Activity for Inactivation of Intracellular Bacteria

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