Magnetic and pH-Sensitive dual actuation of biohybrid microswimmer of targeted drug release suitable for cancer cell microenvironment

Abstract

The chemotherapeutic agents most frequently used in cancer treatment often have limited effectiveness because of their low specificity for tumors and poor therapeutic performance. In addition to the aforementioned therapeutic challenges the drug delivery carriers conjugated with the drug encounter early detection and elimination from the immune system before arriving at the affected area continues to be a significant research focus among researchers. To address this prevalent issue, an effective approach has been developed that leverages the physiological differences between normal and tumor tissue to enhance the efficacy of anticancer drugs. This drug delivery system is designed based on pH-sensitive drug release, ensuring targeted release within cancer cells. In the present study, we have developed a drug carrier called as biohybrid magnetic microswimmer (BMM). The BMM was formed through a three-step process: firstly, bacterial surfaces were functionalized with biotinylated PEG which enables the bacteria to escape the phagocytosis process; secondly, the anticancer drug lenalidomide was PEGylated to enhance solubility; and finally, both complexes were conjugated via streptavidin-biotin interaction. The study investigated bond formation, bacterial viability after drug treatment, pH-dependent release, and cytotoxicity in various cell lines (MCF-7 and THP-1 cells), and the results revealed that the concentration of the drug, released from BMM gradually increased as the pH of the solvent decreased from neutral to acidic, mimicking the surrounding environment of normal cells and cancer cells, respectively, which in turn affects the cancer cell viability negatively. Therefore, BMM shows promise in targeted drug delivery, utilizing magnetic manipulation and pH-triggered release, providing advantages that include bacteria's maneuverability and PEG's stealth properties, enhancing drug efficacy. © 2025 Vietnam National University, Hanoi