Gemcitabine Hydrochloride Drug-Delivery System Based on Folic Acid/Gold Nanoparticle Co-Modified Red Blood Cells for Breast Cancer Treatment

In recent years, the incidence and mortality of breast cancer have shown a rapidly increasing trend worldwide. Gemcitabine hydrochloride (GEM) is clinically the first-line chemotherapeutic drug for breast cancer with excellent antitumor effects. However, the short half-life of GEM and the lack of sustained release effects predispose it to myelosuppression and nephrotoxicity. Red blood cells (RBCs) are primarily used as biological carriers for drug delivery. In view of the shortcomings of GEM in clinical practice, this study constructed a folic acid/gold nanoparticle (AuNPs) surface co-modified RBC carrying the GEM delivery system (FA/Au-GEM-RBCs), based on RBCs as a carrier, aiming to enhance the targeting effect of the carrier. AuNPs could be used as glucose-like oxidase to catalyze glucose oxidation into H2O2, cutting off the source of nutrients to cancer cells, while producing H2O2 damages the RBCs membrane (RBCM) to release drugs. Here, AuNPs were used as a "gated switch" to promote drug release. This DDS has in vitro properties similar to natural RBCs, with the drug loading amount of 10.90 mg/109 RBCs and can circulate for up to 9 days in vivo. In antitumor study studies, FA/Au-GEM-RBCs could target tumor tissues with a tumor inhibition rate of 71.41% ± 8.15%. The delivery system generated multiple reactive oxygen species (ROS), significantly enhancing the effect of tumor treatment. In conclusion, the constructed FA/Au-GEM-RBCs could substantially improve the tumor-killing effect of GEM and deplete the nutrient source at the tumor site. Therefore, this system is expected to achieve synergistic treatment with chemotherapy and starvation therapy and further provide ideas for the treatment of breast cancer.