Researchers develop 'anti-cancer nanoswitch' to block breast and colorectal cancer recurrence and metastasis

Researchers have developed an anti-cancer nanoswitch technology capable of selectively eliminating tumor-promoting extracellular vesicles while generating those that trigger anti-tumor immune responses.

The National Research Foundation of Korea announced Wednesday that a joint research team — comprising Dr. Shim Man-gyu of the Korea Institute of Science and Technology (KIST), Professor Yang Yu-su of Sungkyunkwan University and Professor Kim Jun-seop of Incheon National University — had successfully developed a next-generation anti-cancer immunotherapy that targets and regulates key substances released by cancer cells while boosting patients' immune defenses.

Evidence has been accumulating in the academic community that tumor-derived extracellular vesicles (TEVs) not only promote tumor growth but can also suppress it.

Existing pharmacological approaches, however, have focused mainly on non-selectively disrupting or inhibiting the production of extracellular vesicles. This approach also blocks "beneficial extracellular vesicles" capable of activating anti-cancer immune responses, reducing therapeutic efficacy. Precision control technology was needed — one that could eliminate only the vesicles aiding cancer growth and metastasis while selectively generating immunogenic-phenotype vesicles that activate anti-tumor immunity.

To address this problem, the research team proposed a novel strategy called "Switching TEVs Off and On" and developed EVOTAC, a nanoswitch therapeutic designed to put it into practice.

The therapeutic first resets the tumor microenvironment by targeting and degrading key intracellular proteins involved in tumor-derived vesicle production, thereby blocking their release. When a localized laser is then applied to the tumor site, vesicle production is reactivated — but the tumor cells undergo a photodynamic therapy reaction triggered by a photosensitizer incorporated in the therapeutic, causing them to preferentially generate "immunogenic extracellular vesicles" that induce anti-cancer immunity.

When the team applied this nanoswitch strategy to animal models of triple-negative breast cancer and colorectal cancer, tumors were completely eliminated and anti-cancer immune responses effectively suppressed both recurrence and metastasis.

"This technology constructs a supramolecular nano-platform that self-assembles through intermolecular interactions without a separate drug carrier, simultaneously resolving the limitations of conventional nanomedicines — low drug-loading efficiency, potential carrier toxicity and complex production processes," Shim said. "We hope this will serve as an opportunity to overcome the limitations of existing anti-cancer immunotherapy and open a new treatment paradigm."

The research was supported by the biotech and medical technology development project run by the Ministry of Science and ICT and the National Research Foundation of Korea, and was published in the international biochemistry journal Signal Transduction and Targeted Therapy.