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

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

doi:10.1016/j.nano.2019.102019

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

Nanomedicine. 2019 Aug:20:102019. doi: 10.1016/j.nano.2019.102019. Epub 2019 May 22.

Authors

Xiao Zhi¹, Yanlei Liu¹, Lingnan Lin², Meng Yang¹, Lingxia Zhang³, Li Zhang³, Yangtian Liu⁴, Gabriel Alfranca⁵, Lijun Ma⁶, Qian Zhang⁵, Hualin Fu⁵, João Conde⁷, Xianting Ding⁸, Di Chen⁵, Jian Ni⁵, Jie Song⁵, Daxiang Cui⁹

Affiliations

¹ Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China; School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Institute of Refrigeration and Cryogenics, Shanghai Jiao Tong University, Shanghai, China; National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Gastroenterology, Xi'an Central Hospital, Xi'an, China.
⁴ School of Statistics and Management, Shanghai University of Finance and Economics Yangpu District, Shanghai,China.
⁵ Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.
⁶ Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Queen Mary University London, School of Engineering & Material Science, London, England.
⁸ School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁹ Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China; Institute of Refrigeration and Cryogenics, Shanghai Jiao Tong University, Shanghai, China; National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: dxcui@sjtu.edu.cn.

PMID: 31125676
DOI: 10.1016/j.nano.2019.102019

Abstract

How to eradicate Helicobacter pylori (H. pylori) in vivo with antibiotic resistance owns tremendous clinical requirement. Herein, gold nanostars were conjugated with acid-sensitive cis-aconitic anhydride modified anti-H. pylori polyclonal antibodies, resultant pH sensitive gold nanostars@H. pylori-antibodies nanoprobes (GNS@Ab) were employed for the theranostics of H. pylori in vivo. Photoacoustic imaging confirmed that prepared GNS@Ab could target actively H. pylori in the stomach. GNS@Ab nanoprobes could kill H. pylori in vivo in model animals under NIR laser irradiation, all GNS@Ab nanoprobes could be excreted out of gut within 7 days after oral administration. Gastric local lesion caused by H. pylori restored to normal status within one month. GNS@Ab nanoprobes within therapeutic doses did not damage intestinal bacteria imbalance. Forty clinical specimens of H. pylori with antibiotic resistance were verified validity of GNS@Ab nanoprobes. Prepared oral pH-sensitive GNS@Ab nanoprobes own clinical translational potential in the theranostics of H. pylori in near future.

Keywords: Antibiotic resistance; Gold nanostars; Gut microbiome; Helicobacter pylori; Numerical simulation; Photoacoustic imaging; Photothermal therapy.

Publication types

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

MeSH terms

Administration, Oral
Animals
Antibodies / pharmacology*
Cell Death / drug effects
Elastic Modulus
Female
Gastrointestinal Microbiome* / drug effects
Gold / chemistry*
Helicobacter pylori / drug effects
Helicobacter pylori / physiology*
Humans
Hydrogen-Ion Concentration
Hyperthermia, Induced
Metal Nanoparticles / chemistry*
Metal Nanoparticles / ultrastructure
Mice, Inbred BALB C
Photoacoustic Techniques
Phototherapy
Phylogeny
Polyethylene Glycols / chemistry
Stomach / microbiology
Tissue Distribution / drug effects

Substances

Antibodies
Polyethylene Glycols
Gold