Overcoming antibiotic resistance caused by genetic mutations of Helicobacter pylori with mucin adhesive polymer-based therapeutics.

Herein, we describe the 3'-sialyllactose-polyethyleneimine-chlorine e6 conjugate (3PC), meticulously engineered to effectively target Helicobacter bacteria (H. pylori) within the gastric environment. The composition of 3PC comprises polyethyleneimine, a cationic polymer, 3'-sialyllactose, which exhibits a specific binding affinity for H. pylori surface proteins, and a photosensitizer capable of generating oxygen radicals in response to specific wavelengths. The distinctive feature of 3PC lies in its capacity to enhance interaction with the anionic mucus layer facilitated by electrostatic forces. This interaction results in prolonged residence within the intestinal environment. The extended vacation in the intestinal milieu overcomes inherent limitations that have historically impeded conventional antibiotics from efficiently reaching and targeting H. pylori. 3PC can be harnessed as a potent tool for antibacterial photodynamic therapy, and its versatility extends to addressing the challenges posed by various antibiotic-resistant strains. The exceptional efficacy of 3PC in enhancing intestinal residence time and eradicating H. pylori has been robustly substantiated in animal models, particularly in mice. In summary, 3PC is a formidable agent capable of eradicating H. pylori, irrespective of its antibiotic resistance status, by efficiently penetrating and selectively targeting the mucus layer within the gastric environment.

pH-Responsive Zinc Ion Regulating Immunomodulatory Nanoparticles for Effective Cancer Immunotherapy.

Herein, we introduce a novel approach involving the utilization of a human serum albumin-coated zeolite imidazolate framework-8 containing a photosensitizer (HPZ) that exhibits targeted recognition of the tumor microenvironment, enabling the rapid elevation of zinc ion concentrations while facilitating the controlled release of an encapsulated photosensitizer (PS). At a physiological pH of 7.4, HPZ demonstrates a size of approximately 170 nm, significantly decreasing to less than 10 nm under pH 6.5 acidic conditions. Acid-induced decomposition of HPZ triggers a rapid increase in zinc ion concentration, eliciting potent cytotoxic effects against colorectal, breast, and pancreatic cancers. Additionally, upon laser irradiation, the encapsulated PS within HPZ initiates the generation of reactive oxygen species, synergistically augmenting the cytotoxicity induced by zinc ions. Intravenous administration of HPZ in a CT26 tumor-bearing mouse model resulted in a notable expansion of CD3+CD4+ helper T cells and CD3+CD8+ cytotoxic T cells, accompanied by a reduction in the CD4+CD25+Foxp3+ regulatory T-cell population. These changes led to significant inhibition of tumor growth, highlighting the efficacy of HPZ in this experimental model. Importantly, HPZ exhibits favorable safety characteristics, displaying no toxicity toward vital organs and inducing no weight loss. Thus, HPZ holds immense promise as a standalone treatment or in combination with diverse anticancer immunotherapies, underscoring its potential in the field of anticancer immunotherapy.

Helicobacter pylori-targeting multiligand photosensitizer for effective antibacterial endoscopic photodynamic therapy.

Helicobacter pylori (H. pylori) infection is closely associated with the development of gastric inflammatory diseases and cancer. However, the continued abuse and misuse of antibiotics has accelerated the spread of antibiotic-resistant strains, which poses a tremendous challenge for antibiotic-based H. pylori treatment. In this study, a H. pylori-targeting photodynamic therapy (PDT) system is proposed that multiple 3'-sialyllactose (3SL)-conjugated, poly-l-lysine-based photosensitizer (p3SLP). p3SLP facilitates H. pylori-targeting PDT via the specific interaction between 3SL and sialic acid-binding adhesin (SabA) in the H. pylori membrane. p3SLP can be orally administered to H. pylori infected mice and irradiated using an endoscopic laser system. The gastrointestinal pathological analysis of the H. pylori-infected mice demonstrated significant H. pylori specific antibacterial effects of PDT without side effects to normal tissue. In addition, an anti-inflammatory response was observed at the site of infection after p3SLP treatment. Consequently, this study demonstrates the superior efficacy of anti-H. pylori PDT with p3SLP in H. pylori-infected mice, and this approach shows great potential for replacing antibiotic-based therapy.