A multifunctional nanocomposite coated with a BSA membrane for cascaded nitric oxide therapy

Gas therapy based on nitric oxide (NO) has emerged as a potential therapeutic approach for cancer, and in conjunction with multi-mode combination therapy, offers new possibilities for achieving significant hyperadditive effects. In this study, an integrated AI-MPDA@BSA nanocomposite for diagnosis and treatment was constructed for PDA based photoacoustic imaging (PAI) and cascade NO release. Natural NO donor L-arginine (L-Arg) and photosensitizer (PS) IR780 were loaded into mesoporous polydopamine (MPDA). Bovine serum albumin (BSA) was conjugated to the MPDA to increase the dispersibility and biocompatibility of the nanoparticles, as well as to serve as a gatekeeper controlling IR780 release from the MPDA pores. The AI-MPDA@BSA produced singlet oxygen (¹O₂) and converted it into NO through a chain reaction based on L-Arg, enabling a combination of photodynamic therapy and gas therapy. Moreover, due to the photothermal properties of MPDA, the AI-MPDA@BSA performed good photothermal conversion, which allowed photoacoustic imaging. As expected, both in vitro and in vivo studies have confirmed that the AI-MPDA@BSA nanoplatform has a significant inhibitory effect on cancer cells and tumors, and no apparent systemic toxicity or side effects were detected during the treatment period.