Ultrasound‐Responsive Microfluidic Microbubbles for Combination Tumor Treatment

Abstract Anticancer treatment is a worldwide challenge, and there are constant endeavors in this field to develop intelligent drug delivery systems to improve the therapeutic effect. This paper presents novel ultrasound‐responsive delivery microbubbles (UDMs), with chemotherapeutic‐encapsulated hydrogel shells and therapeutic gas cores. These are developed using microfluidic electrospray to treat pancreatic tumors. As the hydrogel shells are composed of thermo‐sensitive poly(N‐isopropylacrylamide) (PNIPAM), they can contract under mild hyperthermia generated by the acoustic‐wave‐induced oscillation of the encapsulated gas. Thus, by triggering with ultrasound, the chemotherapeutic Gemcitabine (Gem) encapsulated in the hydrogel shells and the hydrogen sulfide (H 2 S) encased in the cores can be controllably released. Based on the UDMs, it is demonstrated that the multiple drug‐loaded microcarriers exhibit an excellent tumor‐killing effect through combination therapy. The Gem and H 2 S coloaded UDMs have good therapeutic efficacy and adaptability in an orthotopic pancreatic implantation tumor model established in mice. These results indicate that the proposed UDMs have a large potential for codelivery of multiple drugs for treating deep‐seated tumors and for realizing combination drug treatment to avoid untoward reactions.