Rhamnolipid-assisted black phosphorus nanosheets with efficient isolinderalactone loading against drug resistant Helicobacter pylori

[Display omitted] •A multi-functional RHL@BP/ISL nanocomposite characterized with BP protection, high capability of drug loading, mucus layer penetration, acid responsive and NIR control release of payloads was developed.•Oral formulation with simply prepared procedures.•Efficient NIR and acid-promoted release of ISL.•Preeminent activity against drug-resistant HP separated from patients. Oral administration remains the main treatment for H. pylori infection, but the acidic environment of the stomach, the biofilm and drug resistance of H. pylori severely impair the antibacterial effect of orally clinical drugs. Here, a multifunctional nanodrug, composed of rhamnolipid-assisted black phosphorus nanocomposite (RHL@BP), is engineered for drug resistant H. pylori (H. pylori-R) treatment. The nanosystem is utilized to efficiently deliver isolinderalactone (ISL), a kind of sesquiterpenoids compound purified from traditional Chinese medicine, exhibiting significantly enhanced antibacterial ability against H. pylori-R under near-infrared (NIR) irradiation. The acid sensitivity of BP and photothermal instability of RHL could trigger the controlled and efficient release of ISL, exhibiting significant synergistic antibacterial activity against H. pylori-R in combined with NIR irradiation. In an H. pylori-R infected mice model, the amount of remnant H. pylori-R in the combination of RHL@BP/ISL and NIR irradiation without antacid group was significantly lower than that of in the conventional triple therapy group (P