The efficacy and safety of pH‐responsive and photothermal‐sensitive multifunctional nanoparticles loaded with cryptotanshinone for the treatment of gastric cancer

Abstract A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti‐gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near‐infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH‐responsive and NIR‐triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti‐GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.