Innovative Oral Nano/Gene Delivery System Based on Engineered Modified <i>Saccharomyces cerevisiae</i> for Colorectal Cancer Therapy

The efficient delivery of RNA-based drugs to solid tumors remains a formidable obstacle. We aim to develop a safe and efficient oral drug delivery system compatible with RNA-based drugs that is urgently needed to overcome challenges such as enzymatic degradation and gastrointestinal barriers to facilitate effective treatment for treating colorectal cancer (CRC). To address these challenges, we utilized engineered modified <i>Saccharomyces cerevisiae</i> to evaluate the delivery efficacy of miR21-antagomir for treating CRC in preclinical mouse models, including adenomatosis polyposis coli mutant transgenic mice <i>Apc</i>^Min/+ and in situ tumor-bearing mice. An orally deliverable gene delivery system, YS@NPs21, was designed. This gene delivery system demonstrated effectively suppressed tumor growth in both <i>Apc</i>^Min/+ and in situ tumor-bearing mice models. This system exhibited tumor-targeting capability, effective inhibition of tumor growth, and low toxicity toward nontumor cells. Successful implementation of this innovative oral drug delivery system could offer a straightforward, safe, and RNA drug-compatible approach to CRC treatment, ultimately improving patient outcomes and reducing medical costs.