Sonosensitizer-doped framework theranostic nanoprobe for enhanced spatiotemporal eradication of helicobacter pylori with photoacoustic imaging guidance.

Helicobacter pylori (H. pylori) infection is the leading cause of gastric cancer. Current antibiotic-based H. pylori suppression therapy suffers from low efficacy, drug resistance, and intestinal flora imbalance, which makes an accurate, controllable, and safe H. pylori inhibition strategy urgent. Here, we present a theranostic nanoprobe, UPE@ZH, which integrates sonodynamic therapy and urease inactivation guided by photoacoustic imaging. The UPE@ZH nanoprobe consists of a sonosensitizer and photoacoustic agent, hematoporphyrin monomethyl ether (HMME), doped into a zeolitic imidazolate framework (ZIF-8) and coated with the pH-responsive polymer Ureido-PEG2000-modified polyacrylic resin (UPE). When administered orally to H. pylori-infected mice, the UPE@ZH nanoprobe collapses gradually in the acidic environment of H. pylori infection, while HMME and zinc ion release occur, resulting in the synergistic eradication of H. pylori through HMME-based sonodynamic therapy and zinc ion-based urease inactivation, under the guidance of photoacoustic imaging. This approach offers a promising, efficient, and safe treatment strategy for H. pylori infection with minimized risk of side effects. STATEMENT OF SIGNIFICANCE: Helicobacter pylori (H. pylori) infection has emerged as a growing public health threat. The current triple antibiotic therapy suffers from limited therapeutic efficacy and carries inherent risks of drug resistance and intestinal microbiota dysbiosis. To address these challenges, we developed a novel strategy for photoacoustic imaging-guided antibiotic-free therapeutic based on a theranostic nanoprobe composed of sonosensitizer-doped zeolitic-imidazolate framework, achieving spatiotemporal and enhanced eradication for H. pylori safely. This study makes not only an important contribution to the treatment of H. pylori-related infections but also has general interest to researchers in a broad range of fields, including bacterial eradication, drug delivery, and in vivo imaging.