Colorectal cancer (CRC) is a highly aggressive disease known to spread rapidly to vital organs. Various therapeutic strategies have been explored for CRC, but current treatments are hindered by significant challenges such as drug toxicity, tumor recurrence, and resistance due to genetic mutations in CRC cells. There is thus an urgent need for new anti-tumor drugs that can effectively treat patients with diverse genetic profiles.
A recent study published in the Genes & Diseases journal by researchers from Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Affiliated Hospital of Jiangnan University, and Southern Medical University introduces a novel third-generation photosensitizer called Ce6-GFFY. This molecule was created by covalently linking a photo-responsive Ce6 compound with a GFFY peptide. In solution, Ce6-GFFY forms stable macroparticles measuring an average of 160 nm in diameter, facilitating targeted penetration into tumors through the enhanced permeability and retention (EPR) effect.
In vitro studies demonstrated that when irradiated with a 660 nm laser, Ce6-GFFY effectively penetrated CRC cells and induced significant reactive oxygen species (ROS) production. Additionally, it was observed that CRT, a well-known hallmark associated with immunogenic cell death (ICD), is highly expressed in CRC cells treated with Ce6-GFFY. This finding suggests the potential of Ce6-GFFY to induce ICD, making it promising for CRC therapy.
In vivo experiments showed that these macroparticles had an extended half-life in mice and were effectively absorbed by tumors. The combination of Ce6-GFFY with laser irradiation significantly activated anti-tumor immunity, enhancing cytotoxic T cell infiltration while reducing the accumulation of myeloid-derived suppressor cells within tumors. This resulted in suppressed growth of both primary and metastatic CRCs.
These results indicate that Ce6-GFFY is a promising agent for treating colorectal cancer with minimal side effects. Unlike traditional treatments, photodynamic therapy (PDT) using Ce6-GFFY can destroy cancer cells regardless of genetic mutations, making it an excellent option for patients who do not respond to existing therapies, including those facing clinical drug resistance.
Overall, the researchers conclude that developing Ce6-GFFY represents a promising new strategy for CRC treatment.
