Antibody-conjugated liposomes loaded with indocyanine green for oral targeted photoacoustic imaging-guided sonodynamic therapy of Helicobacter pylori infection.

Abstract

Helicobacter pylori is a causative factor of various gastrointestinal tract diseases. As clinical antibiotic-based therapy for H. pylori infection might induce bacterial drug resistance, the in vivo eradication of H. pylori remains a huge challenge. In the present study, monoclonal antibody-conjugated liposomes loaded with indocyanine green (ICG) (HpAb-LiP-ICG) were successfully developed for targeted photoacoustic (PA) imaging-guided sonodynamic therapy (SDT) of H. pylori infection in vivo. HpAb-LiP-ICG showed high stability and favorable biocompatibility in acidic environment (pH 1.5) and was used for treating H. pylori-infected mice through oral administration. PA imaging showed that HpAb-LiP-ICG could precisely recognize and target H. pylori in the stomach. Following the targeting of HpAb-LiP-ICG to H. pylori, ICG was activated to generate singlet oxygen (¹O₂) for eliminating H. pylori under ultrasound (US) irradiation. Pathological analysis revealed that the HpAb-LiP-ICG-mediated SDT eradicated H. pylori without unintended toxicity to normal tissues. In conclusion, the HpAb-LiP-ICG-mediated SDT might shed new light on treating H. pylori infection, indicating the clinical translational prospects of this therapy in near future. STATEMENT OF SIGNIFICANCE: Traditional antibiotic-based therapy for Helicobacter pylori infections suffers from the risk of drug resistance. To meet this challenge, a monoclonal antibody-conjugated nanoliposome loaded with indocyanine green (ICG) (HpAb-LiP-ICG) was successfully developed, and efficient eradication of H. pylori was achieved in vivo by visual sonodynamic therapy (SDT). HpAb-LiP-ICG exhibited biocompatibility, targeting, and stability in the acidic microenvironment. Under ultrasound (US) irradiation in vitro, the HpAb-LiP-ICG nanoliposomes accumulated on the surface of H. pylori were activated to produce adequate singlet oxygen (¹O₂) to eliminate H. pylori. Gastric mucous tissues infected with H. pylori recovered to the normal state after HpAb-LiP-ICG-mediated SDT without side effects, thus highlighting the clinical translational prospects of the prepared HpAb-LiP-ICG nanoliposome in near future.