A team of Korean researchers has developed a new nanotherapy targeting hard-to-treat breast cancer. This therapy directly breaks down cancer cells and amplifies the immune response.
On the 29th, the National Research Foundation of Korea announced that a joint research team, led by Senior Researcher Shim Man-kyu from the Korea Institute of Science and Technology (KIST) and Professor Park Ju-ho from Konkuk University, has developed ‘NanoTAC.’ This therapy, aimed at treating triple-negative breast cancer, combines Proteolysis-Targeting Chimera (PROTAC) technology with Photodynamic Therapy (PDT). NanoTAC, a concept blending Nanomedicine and PROTAC, features a dual-action mechanism that regulates cancer cell metabolism and enhances the immune response.
Triple-negative breast cancer is a type characterized by the absence of both hormone receptors and the ‘HER2’ protein. It is difficult to treat as it does not respond well to conventional anticancer drugs and carries a high risk of metastasis and recurrence. While immunotherapy has recently emerged as an alternative, its effectiveness is limited by the ability of cancer cells to evade the immune response. Similarly, the efficiency of photodynamic therapy is hindered by the hypoxic environment and excessive glycolysis (the process of glucose breakdown) within cancer cells.
To overcome these challenges, the research team designed a nanotherapy in the form of a supramolecular self-assembly. This assembly is based on a PROTAC, which selectively degrades proteins involved in immune metabolism, and is co-loaded with a photosensitizer. A key feature is its formation through intermolecular interactions without a separate carrier, which is advantageous for mass production.
Experimental results in an animal model of triple-negative breast cancer showed that NanoTAC selectively accumulated in the tumor area. It was then broken down by tumor-specific enzymes, releasing the PROTAC and the photosensitizer. The PROTAC subsequently inhibited glycolysis within the cancer cells and improved the hypoxic conditions. When exposed to light, the resulting photodynamic reaction promoted the activation of immune cells, effectively suppressing tumor growth, recurrence, and metastasis.
Senior Researcher Shim Man-kyu stated, “We maximized the immunogenicity within cancer cells through the synergistic effect of PROTAC-based protein degradation and photodynamic therapy.” He added, “This NanoTAC technology has great potential to be developed into a new anticancer immunotherapy platform applicable to intractable cancers.” The research findings were published in the international journal ‘Signal Transduction and Targeted Therapy’ on the 26th.
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- doi.org/10.1038/s41392-025-02405-6
