Integration of temperature-sensitive hydrogels loaded with realgar and magnetic particles for lung cancer diagnosis and treatment

IntroductionLung cancer has a poor prognosis with traditional treatments. Realgar (AS4S4), a traditional Chinese medicine, exhibits chemotherapeutic efficacy. However, its low solubility, complex dosage form, and limited therapeutic efficacy hinder its further application in lung cancer.MethodsIn this study, AS4S4 was chemically synthesized using hydrochloric acid to disrupt the bonding between AS and NH2, producing realgar nanoclusters that improved solubility and reduced side effects. Simultaneously, Fe3O4 nanoparticles were introduced, and intelligent temperature-sensitive hydrogels were utilized to combine these two performance nanomaterials, developing a local injection nano-diagnosis and treatment unit (AS4S4/Fe3O4@Gel) that integrates chemotherapy with alternating current magnetic field (ACMF) induction hyperthermia. The morphological characteristics, thermal stability, and controlled release of AS4S4/Fe3O4@Gel were assessed. After processing the Lewis cells, the CCK-8 method, hemolysis test, EdU method, cell apoptosis test, reactive oxygen species detection, and cellular ultrastructure analysis were used to evaluate the biological effects. Western blot was employed to detect Bcl-2, BAX, GPX4, and HO-1 protein expression in cells. After injecting the gel system into the transplanted tumor, in vivo imaging, near-infrared thermography, and the antitumor effect were studied.ResultsAS4S4/Fe3O4@Gel, which exhibits fluorescence and magnetic inductive hyperthermia, was successfully developed. The gel system, which has good hemocompatibility, possesses ideal temperature sensitivity. It can transform from liquid to solid within a specific temperature range, and the drug release rate about 80% within 3 h at 42 degrees C. Cell experiments showed that the combination of AS4S4/Fe3O4@Gel and ACMF induced the highest levels of apoptosis and ferroptosis. AS4S4/Fe3O4@Gel in vivo displayed good fluorescence characteristics and a magnetocaloric effect. The combination therapy group significantly decreased the expression levels of Ki-67, CD31, E-cadherin, Bcl-2, and GPX4 proteins, indicating that combination therapy can better exert antitumor effects. At the same time, AS4S4/Fe3O4@Gel had no damage to normal organs.ConclusionThe prepared AS4S4/Fe3O4@Gel in this study can exert synergistic antitumor activity in combination with ACMF under bimodal imaging guidance and represents a potential clinical treatment for lung cancer.