Colorectal cancer (CRC) is an extremely aggressive disease known for its tendency to metastasize to critical organs within the body. Various therapeutic strategies have been attempted in clinical settings, but these treatments are currently limited by several challenges, including drug toxicity, tumor recurrence, and resistance due to gene mutations in CRC cells. Consequently, there is a pressing need for innovative anti-tumor drugs capable of effectively treating CRC 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 third-generation photosensitizer called Ce6-GFFY. This novel compound was developed through the covalent linkage of a photo-responsive Ce6 molecule with a GFFY peptide. In solution, Ce6-GFFY forms stable macroparticles averaging 160 nm in size, which facilitates targeted tumor penetration via the enhanced permeability and retention (EPR) effect.
In vitro studies conducted by the researchers revealed that Ce6-GFFY effectively penetrated CRC cells upon irradiation with a 660 nm laser. Moreover, significant production of reactive oxygen species (ROS) was observed in these cells following treatment. Additionally, classical hallmark cyclooxygenase-2 transcription factor (CRT), which acts as an “eat-me” signal promoting immune recognition and clearance, was highly expressed in CRC cells treated with Ce6-GFFY. This finding suggests that Ce6-GFFY can induce immunogenic cell death (ICD), hinting at its promising potential for CRC therapy.
In vivo experiments further supported these findings. The macroparticles showed a prolonged half-life in mice, indicating effective drug uptake and an extended therapeutic window. When used in conjunction with laser irradiation, Ce6-GFFY significantly activated anti-tumor immunity by promoting the infiltration of cytotoxic T cells into tumors while inhibiting the accumulation of myeloid-derived suppressor cells. This dual action resulted in the suppression of both primary and metastatic CRC growth.
The researchers highlight that these findings suggest Ce6-GFFY could be a promising agent for CRC therapy, potentially minimizing side effects compared to traditional treatments. Unlike conventional therapies, photodynamic therapy (PDT) using Ce6-GFFY can target cancer cells regardless of genetic mutations, making it a versatile option for patients who are resistant to existing treatments.
In conclusion, the development of Ce6-GFFY represents a novel and promising strategy in CRC treatment. This research underscores its potential to revolutionize current therapeutic approaches by offering an effective means to address the challenges posed by diverse genetic profiles in CRC cells.
