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

Ruhao Wang; Cunfeng Song; Ang Gao; Qianwen Liu; Wenbin Guan; Jiawei Mei; Lijun Ma; Daxiang Cui

doi:10.1016/j.actbio.2022.02.031

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

Acta Biomater. 2022 Apr 15:143:418-427. doi: 10.1016/j.actbio.2022.02.031. Epub 2022 Feb 25.

Authors

Ruhao Wang¹, Cunfeng Song², Ang Gao³, Qianwen Liu³, Wenbin Guan⁴, Jiawei Mei⁵, Lijun Ma⁶, Daxiang Cui⁷

Affiliations

¹ Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China.
² Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China; National Engineering Center for Nanotechnology, Collaborative Innovational Center for System Biology, 28 Jiangchuan Road, Shanghai 200241, China. Electronic address: songcf@sjtu.edu.cn.
³ Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China; National Engineering Center for Nanotechnology, Collaborative Innovational Center for System Biology, 28 Jiangchuan Road, Shanghai 200241, China.
⁴ Department of Pathology, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine,1665 Kongjiang RD, Shanghai 200092, China.
⁵ Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
⁶ Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xian Xia Road, Shanghai 200336, China.
⁷ Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China; National Engineering Center for Nanotechnology, Collaborative Innovational Center for System Biology, 28 Jiangchuan Road, Shanghai 200241, China. Electronic address: dxcui@sjtu.edu.cn.

PMID: 35219867
DOI: 10.1016/j.actbio.2022.02.031

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.

Keywords: Helicobacter pylori; Indocyanine green; Photoacoustic imaging; Sonodynamic therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Antibodies, Monoclonal
Helicobacter Infections* / drug therapy
Helicobacter pylori*
Indocyanine Green / pharmacology
Liposomes
Mice
Photoacoustic Techniques*
Singlet Oxygen

Substances

Anti-Bacterial Agents
Antibodies, Monoclonal
Liposomes
Singlet Oxygen
Indocyanine Green