Oral pH sensitive GNS@ab nanoprobes for targeted therapy of Helicobacter pylori without disturbance gut microbiome

Zhi, Xiao; Liu, Yanlei; Lin, Lingnan; Yang, Meng; Zhang, Lingxia; Zhang, Li; Liu, Yangtian; Alfranca, Gabriel; Ma, Lijun; Zhang, Qian; Fu, Hualin; Conde, João; Li, Yiyang; Chen, Di; Ni, Jian; Song, Jie; Cui, Daxiang

doi:10.1016/j.nano.2019.102019

Cited by 46 publications

(43 citation statements)

References 22 publications

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“…As physical therapeutics has come of age, we have witnessed a great transformation in the quest for antibacterial innovations. Much focus has turned toward physical (e.g., heat [ 9 , 10 ], X-ray irradiation [ 11 ], and high-pressure [ 12 ]) inactivation of microbial cells because they are amenable to MDR pathogens and typically have less potential to induce resistance. Comparatively, light-driven photodynamic therapy presents an ever-attractive methodology against bacterial infections by virtue of its intrinsic safety and noninvasiveness [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Beyond Antibiotics: Photo/Sonodynamic Approaches for Bacterial Theranostics

Pang

Zhu

et al. 2020

Nano-Micro Lett.

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Rapid evolution and propagation of multidrug resistance among bacterial pathogens are outpacing the development of new antibiotics, but antimicrobial photodynamic therapy (aPDT) provides an excellent alternative. This treatment depends on the interaction between light and photoactivated sensitizer to generate reactive oxygen species (ROS), which are highly cytotoxic to induce apoptosis in virtually all microorganisms without resistance concern. When replacing light with low-frequency ultrasonic wave to activate sensitizer, a novel ultrasound-driven treatment emerges as antimicrobial sonodynamic therapy (aSDT). Recent advances in aPDT and aSDT reveal golden opportunities for the management of multidrug resistant bacterial infections, especially in the theranostic application where imaging diagnosis can be accomplished facilely with the inherent optical characteristics of sensitizers, and the generated ROS by aPDT/SDT cause broad-spectrum oxidative damage for sterilization. In this review, we systemically outline the mechanisms, targets, and current progress of aPDT/SDT for bacterial theranostic application. Furthermore, potential limitations and future perspectives are also highlighted.

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Section: Introductionmentioning

confidence: 99%

Beyond Antibiotics: Photo/Sonodynamic Approaches for Bacterial Theranostics

Pang

Zhu

et al. 2020

Nano-Micro Lett.

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“…One way to achieve this may be through well-controlled local photothermal/magnetic thermal treatments using nanomaterials which have shown early promise in suppressing bacterial growths ( Mocan et al, 2017 ; Chen et al, 2018 ), including H. pylori ( Wu et al, 2019 ). It is recently reported that gold nanostars@ H. pylori -antibodies nanoprobes could target and kill H. pylori in the stomach in model animals under near-infrared laser irradiation ( Zhi et al, 2019 ). However, feasibility and safety of sustained localized thermal treatment within human gastric mucosa need to be ascertained in a clinical setting in order for it to become a viable strategy for H. pylori eradication.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in environmental conditions lead to alterations in transcriptomic profiles of H. pylori ( Thompson et al, 2003 ; De la Cruz et al, 2017 ). Previous evidence has demonstrated local nanoparticle heating inhibits H. pylori growth and virulence as a potential alternate approach to treating H. pylori infections ( Wu et al, 2019 ; Zhi et al, 2019 ). Whilst temperature differences have led to changes leading to increased antibiotic resistance in other bacteria species ( Liang et al, 2016 ; Loughman et al, 2016 ; De Silva et al, 2018 ), the effects of temperature on antibiotic resistance and transcriptomic changes in H. pylori have not been investigated previously.…”

Section: Introductionmentioning

confidence: 99%

Effect of Temperature on Metronidazole Resistance in Helicobacter pylori

et al. 2021

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Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-sequencing to identify differentially expressed genes (DEGs) associated with increased temperature. Transcriptional pathways involved in temperature-driven metronidazole resistance changes were analyzed through bioinformatic and literature curation approaches. We showed that H. pylori growth was inhibited at 41°C and inhibition was more apparent with prolonged incubation. Resistance to metronidazole was also reduced—minimum inhibitory concentration for metronidazole decreased from > 256 μg/ml at 37°C to 8 μg/ml at 41°C after culturing for 3 days. RNA-sequencing results, which were highly concordant within treatment conditions, revealed more than one third of genes (583/1,552) to be differentially expressed at increased temperatures with similar proportions up and down-regulated. Quantitative real-time PCR validation for 8 out of 10 DEGs tested gave consistent direction in gene expression changes. We found enrichment for redox and oxygen radical pathways, highlighting a mechanistic pathway driving temperature-related metronidazole resistance. Independent literature review of published genes associated with metronidazole resistance revealed 46 gene candidates, 21 of which showed differential expression and 7 out of 9 DEGs associated with “redox” resistance pathways. Sanger sequencing did not detect any changes in genetic sequences for known resistance genes rdxA, frxA nor fdxB. Our findings suggest that temperature increase can inhibit the growth and reduce H. pylori resistance to metronidazole. Redox pathways are possible potential drivers in metronidazole resistance change induced by temperature. Our study provides insight into potential novel approaches in treating antibiotic resistant H. pylori.

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“…The application of AuNUs is not limited to cancer therapy, but may also help to eradicate various pathogens that are linked to tumorigenesis or other health conditions. For instance, antibiotic-resistant Helicobacter pylori represents a potential clinical target for AuNUs [29]. This pathogen promotes inflammation and increases the risk for gastric cancer.…”

Section: Diseases and Disorders That Could Benefit From Aunu-based Therapymentioning

confidence: 99%

“…This pathogen promotes inflammation and increases the risk for gastric cancer. When administered orally, pH-sensitive AuNUs can eliminate H. pylori in the stomach of living experimental mice [29]. The AuNUs were excreted within 7 days, suggesting a safe route to prevent AuNU accumulation [29].…”

Section: Diseases and Disorders That Could Benefit From Aunu-based Therapymentioning

confidence: 99%