Enhancing chemotherapy for colorectal cancer: EGFR-conjugated ferritin nanocages for targeted doxorubicin delivery.

Biomimetic nanoparticles, exemplified by ferritin, have emerged as a novel approach in drug delivery systems, designed to improve both the biocompatibility of drugs and their targeting. The clinical application of doxorubicin (Dox) is impeded by systemic toxicity and multidrug resistance, emphasising the necessity for innovative delivery platforms. In this research, we proposed the hypothesis that a protein-based nanocage, decorated with an anti-epidermal growth factor receptor (EGFR) peptide as a targeting ligand on its surface, has the potential to enhance the targeted delivery of Dox while reducing systemic toxicity. In vitro studies with the CT26 murine colorectal cancer (CRC) cell line demonstrate marked toxicity and suppression of cell migration, indicating the potential of these nanocages to inhibit metastasis. In vivo experiments using established tumour-bearing mice further confirm the therapeutic efficacy of these nanocages, showing a significant reduction in tumour growth, prolonged survival and diminished systemic toxicity compared to free Dox. In addition, cytokine analysis underscored the immunomodulatory capabilities of M1-linker-QRH in the context of cancer treatment. By addressing critical challenges in drug delivery, this platform holds promise for advancing precision oncology and improving clinical outcomes for patients with CRC.