Living Biohybrid Hydrogels for Co-Delivery of Oxygen, Anti-Cancer Drugs, and Probiotics: Effects on Cancer and Healthy Cell Viability.

In recent studies, oxygen (O2) delivery biomaterials have been developed to reduce hypoxia-induced problems in, e.g., tumor tissues. However, none of these studies have used inhibitory effects of probiotics in combination therapies with O2 and anticancer drugs for advanced cancer treatment applications. In this study, we report a new probiotic-enriched 3D-printed biomaterial (3D-BioHybrid-DOX/SPEP) that is capable of O2, probiotic, and acidic pH (pH 6.0) sensitive anticancer drug (Doxorubicin = DOX) co-release. 3D-BioHybrid-DOX/SPEP shows sustained O2 and pH-responsive anticancer drug release over 14 days. The release of short-chain fatty acids, including butyric acid, was detected on days 1 and 7 of incubation, indicating that the O2 delivery component of the system supports probiotic viability while mitigating the toxic effects of DOX. The CFU results show that the 3D-BioHybrid-DOX/SPEP supports probiotic viability at 1 and 7 days of incubation. In vitro cell experiments indicate that the healthy cell viability is ca. 2 times higher than cancer cells after 1 and 7 days of incubation at hypoxia conditions in 3D-BioHybrid-DOX/SPEP due to the co-administration of O2, DOX, and probiotics.