Abstract

SiRNA has been widely studied in cancer gene silencing over the last 25 years. However, few siRNA-based therapeutics have been approved by the FDA. An RNA-micelle platform provides a powerful therapeutic tool through simple one-step, high-yield production that is capable of efficient colorectal cancer lung metastasis treatment, a current lethal condition with a short survival rate post-diagnosis. Here, it is reported that the use of RNA-micelles co-carrying siRNA and nucleoside analogues to completely inhibit lung metastasis of colorectal cancer (CRC). The major advantage of the RNA-micelle is the successful co-delivery of siRNA and chemotherapeutic agent in a single delivery vehicle while specifically targeting CRC cells via incorporation of an oncogenic surface receptor ligand. It was found that RNA-micelles could combine to silence survivin protein expression via siRNA delivery, which in turn increased the efficacy of the delivered chemotherapeutic agent. Both siRNA and high-payload nucleoside-analogues were incorporated onto a single micelle, which remained stable during in vivo circulation, rather than individual RNA nanoparticles, thus generating this advantageous synergistic cancer regression. This platform provides a powerful therapeutic tool to address colorectal cancer lung metastasis, a currently serious, lethal disease that has a very poor prognosis following diagnosis.

Document Type

Article

Publication Date

2026

Notes/Citation Information

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2026 The Author(s). Advanced Functional Materials published by Wiley-VCH GmbH

Digital Object Identifier (DOI)

https://doi.org/10.1002/adfm.202521863

Funding Information

This work was supported by the National Cancer Institute grant R01 CA293945 (P.G.), the NIH Eye institute R01 EY031452 (P.G.), and The Ohio State University President’s Research Excellence (PRE) Catalyst Award. The authors are solely responsible for the content of this work, which may not necessarily represent the official views of the NIH. The work was partilly supported by Sylvan G. Frank Endowed Chair fund for Pharmaceutics and Drug Delivery at OSU to P.G. Zetasizer nano-ZS is kindly provided by Dr. Zachary Schultz at the Ohio State University.

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