Wang Ruhao, Song Cunfeng, Gao Ang, Liu Qianwen, Guan Wenbin, Mei Jiawei, Ma Lijun, Cui Daxiang
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.
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.
Acta Biomater. 2022 Apr 15;143:418-427. doi: 10.1016/j.actbio.2022.02.031. Epub 2022 Feb 25.
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 (O) 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 (O) 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.
幽门螺杆菌是多种胃肠道疾病的致病因素。由于基于临床抗生素的幽门螺杆菌感染治疗可能会诱导细菌耐药性，因此在体内根除幽门螺杆菌仍然是一项巨大的挑战。在本研究中，成功开发了负载吲哚菁绿（ICG）的单克隆抗体偶联脂质体（HpAb-LiP-ICG），用于体内幽门螺杆菌感染的靶向光声（PA）成像引导声动力疗法（SDT）。HpAb-LiP-ICG在酸性环境（pH 1.5）中表现出高稳定性和良好的生物相容性，并通过口服给药用于治疗幽门螺杆菌感染的小鼠。PA成像显示，HpAb-LiP-ICG可以精确识别并靶向胃中的幽门螺杆菌。在HpAb-LiP-ICG靶向幽门螺杆菌后，ICG被激活以产生活性单线态氧（O），用于在超声（US）照射下消除幽门螺杆菌。病理分析表明，HpAb-LiP-ICG介导的SDT根除了幽门螺杆菌，而对正常组织没有意外毒性。总之，HpAb-LiP-ICG介导的SDT可能为治疗幽门螺杆菌感染带来新的思路，表明该疗法在不久的将来具有临床转化前景。重要性声明：传统的基于抗生素的幽门螺杆菌感染治疗存在耐药风险。为应对这一挑战，成功开发了负载吲哚菁绿（ICG）的单克隆抗体偶联纳米脂质体（HpAb-LiP-ICG），并通过可视化声动力疗法（SDT）在体内实现了幽门螺杆菌的有效根除。HpAb-LiP-ICG在酸性微环境中表现出生物相容性、靶向性和稳定性。在体外超声（US）照射下，聚集在幽门螺杆菌表面的HpAb-LiP-ICG纳米脂质体被激活，产生足够的单线态氧（O）以消除幽门螺杆菌。经HpAb-LiP-ICG介导的SDT治疗后，感染幽门螺杆菌的胃黏液组织恢复正常状态且无副作用，从而突出了所制备的HpAb-LiP-ICG纳米脂质体在不久的将来的临床转化前景。
