Innovative Oral\nNano/Gene Delivery System Based on\nEngineered Modified Saccharomyces cerevisiae for Colorectal Cancer Therapy

The efficient delivery of RNA-based drugs to solid tumors\nremains\na formidable obstacle. We aim to develop a safe and efficient oral\ndrug delivery system compatible with RNA-based drugs that is urgently\nneeded to overcome challenges such as enzymatic degradation and gastrointestinal\nbarriers to facilitate effective treatment for treating colorectal\ncancer (CRC). To address these challenges, we utilized engineered\nmodified Saccharomyces cerevisiae to\nevaluate the delivery efficacy of miR21-antagomir for treating CRC\nin preclinical mouse models, including adenomatosis polyposis coli\nmutant transgenic mice <i>Apc</i><sup>Min/+</sup> and in\nsitu tumor-bearing mice. An orally deliverable gene delivery system,\nYS@NPs21, was designed. This gene delivery system demonstrated effectively\nsuppressed tumor growth in both <i>Apc</i><sup>Min/+</sup> and in situ tumor-bearing mice models. This system exhibited tumor-targeting\ncapability, effective inhibition of tumor growth, and low toxicity\ntoward nontumor cells. Successful implementation of this innovative\noral drug delivery system could offer a straightforward, safe, and\nRNA drug-compatible approach to CRC treatment, ultimately improving\npatient outcomes and reducing medical costs.