Nanobiomaterials Based Sonodynamic Therapy for Treament of Helicobacter pylori Infections: A Review

Mengfan Li^{¹^,²^,^§}, Yingli Gong^{¹^,²^,^§}, Tielou Chen^{⁴^,^§}, Lei Lu^¹, Xiuwen Ding^¹, Cuimin Chen^¹, Yan Wu^²(), Tinglin Zhang^{¹^,³}(), Jie Gao^{¹^,²^,³}()

1Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China

2College of Life Science, Mudanjiang Medical University, Mudanjiang157011, China

3Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai 200433, China

4Department of Stomatology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China

^§These authors contributed equally to this work.

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Abstract

Helicobacter pylori (HP) is a helical-shaped bacterium that inhabits the human stomach and is associated with various pathologies, including gastritis, gastric ulcers, and gastric cancer. HP infection is the largest contributor to gastric cancer, and approximately 90% of non-cardia gastric cancers are related to HP infection. As HP gastritis is an infectious disease, eradicating HP is an effective measure to prevent gastric cancer. Traditional triple therapy has demonstrated limited efficacy due to the emergence of antibiotic resistance and disruption of the intestinal microbiota. Sonodynamic therapy is an innovative nonantibiotic approach that utilizes a sonosensitizer to generate reactive oxygen species in response to ultrasound, effectively targeting pathogenic microorganisms; recent advancements have highlighted its potential for the treatment of HP infection. This article reviews recent developments in ultrasound-assisted biomaterials designed to combat HP while simultaneously preserving intestinal microecology. Furthermore, it discusses the integrated mechanisms underlying both the anti-HP effects and the maintenance of intestinal microecology. These strategies provide novel insights into overcoming the limitations associated with traditional antibiotic therapies and establish a foundation for future clinical applications.

Keywords

Helicobacter pylori (HP)ultrasonic sonodynamic therapy biomaterials intestinal microbiota

References

[1]

P. Malfertheiner, F. Megraud, T. Rokkas, et al. Management of Helicobacter pylori infection: The maastricht VI/Florence consensus report. Gut, 2022, 71: 1724−1762. https://doi.org/10.1136/gutjnl-2022-327745

Sound sensitizer	Ultrasound parameters	Antibacterial effects of SDT	Ref.
Organic sound sensitizer
CNPS-ICG	1 MHz, 1.56 W/cm², 1 min	Removed periopathogen biofilm on the surface of the titanium dental implant under diode laser irradiation + US	[71]
HpAb-LiP-ICG	1 MHz, 1.5 W/cm², 10 min	Activated Ab-LiP-ICG produces singlet oxygen (¹O₂), which can effectively damage the cell membrane and internal structure of bacteria.	[72]
HMME	1 MHz, 3 W/cm², 10 min	Treating P. gingivalis with ultrasound at a concentration of 40 μg/mL HMME at 3 W/cm² for 10 minutes reduced CFU (colony forming unit) by 4.7 lg (p < 0.01).	[73]
Fe-HMME@DHA@MPN	1 MHz, 1.5 W/cm², 70% cycle, 4 min	Ultrasonic treatment, improved biofilm activity, with a removal rate of 94.5%	[74]
Fe@UCNP-HMME	2 W/cm², 10 min	Achieved 0% of relative viability	[75]
Ver-PLGA@Lecithin	1 MHz, 0.5 W/cm², 70% cycle, 10 min	Under the action of ultrasound, VerPLGA@Lecithin nanoparticles can generate ROS and effectively kill HP	[32]
Inorganic sound sensitizer
PtCu-PEG NPs	40 kHz, 3 W/cm², 50% cycle, 8 min	The partial oxygenation formed on the surface of the PtCu NPs endows them with good Fenton-like catalytic performance and superior GSH-depleting ability, thus enhancing reactive oxygen species generation.	[76]
PPAF	1 MHz, 1 W/cm², 50% cycle, 2 min	Penetrate the mucous layer, target HP, destroy the biofilm, and show excellent bactericidal ability.	[77]
Pd@Pt-T790	1 MHz, 0.97 W/cm², 50% cycle, 8 min	Nearly 100% of the bacteria were killed	[78]

Materials	Does	Ultrasound parameters	Antibacterial rate	Antibiotic type	Antibacterial effect	Ref.
* Triple therapy dose: omeprazole: 400 μmol/kg, amoxicillin: 28.5 mg/kg, clarithromycin:14.3 mg/kg.
HpAb-LiP-ICG	In vitro: 200 μg/mLIn vivo: 2.5 mg/kg	1 MHz, 1.5 W/cm², 10 min	In vitro: 99.9%In vivo: 99%	—	—	[72]
Fe-HMME@DHA@MPN	In vitro: 40 μg/mLIn vivo: 30 mg/kg	1 MHz, 1.5 W/cm², 70% cycle, 4 min	In vitro: 100%In vivo: 99%	Triple therapy OAC	Equality	[74]
Ver-PLGA@Lecithin	In vitro: 100 μg/mLIn vivo: 10 mg/ml	1 MHz, 0.5 W/cm², 70% cycle, 10 min	In vitro: 99.9%In vivo: 50 times lower than the control group	Triple therapy OAC	Equality	[32]
PPAF	In vitro: 200 μg/mLIn vivo: 30 mg/kg	1 MHz, 1 W/cm², 50% cycle, 2 min	In vitro: 99%In vivo: 10 times lower than the US group	Triple therapy OAC	Antibiotics better	[77]
ICG@FCS	In vitro: 200 μg/mLIn vivo: 30 mg/kg	1 MHz, 1.5 W/cm², 10 min	In vitro: 99%In vivo: 10 times lower than the US group	Triple therapy OAC	SDT better	[83]