Exosome-immobilized porous microspheres for efficiently combined and prolonged cancer treatment

It is crucial to find optimally combined anticancer drug treatments among diverse therapeutics and deliver them simultaneously in a prolonged manner for efficient tumor therapy. In this study, we investigated the novel combined treatment strategy of doxorubicin (Dox) and TGF-β receptor 1 kinase inhibitor (SD208) through the fabrication of exosome (EXO)-immobilized porous microspheres to achieve efficient and sustained anticancer effects. The combined treatment of Dox and SD208 exhibited significant improvements in anticancer efficacy compared to Dox treatment alone in both breast cancer cells (MCF-7) and lung cancer cells (A549). After the Dox and SD208 co-encapsulated EXOs (combiEXOs; ~ 80 nm) were immobilized onto the surface of cationic porous microspheres (PM) through simple electrostatic interactions, the attached combiEXOs were released in a sustained manner over 120 h. Furthermore, combiEXOs onto PMs (PM-combiEXO) effectively induced significant apoptosis in A549 cells and suppressed the proliferation of A549 cells for 5 days with minimal toxicity to fibroblasts. Taken together, the developed PM-combiEXOs significantly improved the anticancer effects in A549 cells in a sustained manner with minimal nonspecific toxicity, demonstrating potential applicability across a wide range of cancers for diverse combined treatments with anticancer drugs.