image: (A) Schematic diagram of Ce6-GFFY synthesis. DCC, N, N0-dicyclohexylcarbodiimide; DMAP, 4-dimethylaminopyridine; CH2CL2, dichloromethane. (B) The size distribution of Ce6-GFFY macroparticles was analyzed using DLS. d, diameter; PDI, polydispersity index; DLS, dynamic light scattering. The data are representative of five independent experiments. (C) The Zeta potential of Ce6-GFFY macroparticles was analyzed using DLS. Blank, PBS. The data are representative of five independent experiments. (D) Ce6-GFFY macroparticle image was photographed by transmission electron microscopy. Scar bar, 100 nm. (E, F) Particle size (E) and polydispersity index (F) of Ce6-GFFY macroparticles incubated at 37 °C at different times as indicated was detected by DLS. The data are representative of five independent experiments. (G) Particle size of Ce6-GFFY incubated at room temperature (normal) or underwent - 80 °C /37 °C freezing-thawing (Freeze-Melt) was detected by DLS. The data are representative of five independent experiments.
Credit: Wei Qiao, Shuxin Li, Linna Luo, Meiling Chen, Xiaobin Zheng, Jiacong Ye, Zhaohui Liang, Qiaoli Wang, Ting Hu, Ling Zhou, Jing Wang, Xiaosong Ge, Guokai Feng, Fang Hu, Rongbin Liu, Jianjun Li and Jie Yang
Colorectal cancer (CRC) is a highly malignant disease that readily metastasizes to vital organs. Many strategies have been employed for clinical CRC therapy. However, current treatments face significant limitations, such as drug toxicity, tumor recurrence, and drug resistance due to gene mutations in CRC cells. Therefore, there is an urgent need to develop novel anti-tumor drugs that can effectively treat CRC patients with diverse genetic profiles.
This research, published in the Genes & Diseases journal by a team from the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Affiliated Hospital of Jiangnan University, and Southern Medical University, focuses on a third-generation photosensitizer, Ce6-GFFY. The researchers developed this novel molecule by covalently combining a photo-responsive Ce6 molecule with a GFFY peptide. Ce6-GFFY forms stable macroparticles with an average size of 160 nm in solution, enabling targeted tumor penetration through the enhanced permeability and retention (EPR) effect.
In the in vitro studies, Ce6-GFFY demonstrated effective penetration and induced significant ROS production in CRC cells upon irradiation with a 660 nm laser. Furthermore, results showed that CRT, a classical hallmark that acts as an “eat-me” signal, is highly expressed in Ce6-GFFY-treated CRC cells. This suggests that Ce6-GFFY can effectively induce immunogenic cell death (ICD), indicating its promising potential for CRC therapy.
In the in vivo studies, the macroparticles exhibited a prolonged half-life in mice, demonstrating effective drug uptake and an extended therapeutic window. The combined use of Ce6-GFFY and laser irradiation significantly activated anti-tumor immunity by promoting cytotoxic T cell infiltration while inhibiting the accumulation of myeloid-derived suppressor cells in tumors, thereby suppressing the growth of both primary and metastatic CRCs. These findings suggest that Ce6-GFFY is a promising agent for CRC therapy with minimal side effects.
Unlike traditional treatments, photodynamic therapy (PDT) with Ce6-GFFY can destroy cancer cells regardless of genetic mutations, making it a versatile therapy option for patients who cannot be treated with any existing therapeutics, including those with clinical drug resistance. In conclusion, the researchers highlight that the development of Ce6-GFFY represents a promising new strategy for the treatment of colorectal cancer.
Reference
Title of Original Paper: Ce6-GFFY is a novel photosensitizer for colorectal cancer therapy
DOI: https://doi.org/10.1016/j.gendis.2024.101441
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