Supramolecular Nanofibers of Curcumin for Highly Amplified Radiosensitization of Colorectal Cancers to Ionizing Radiation

Development of highly efficient radiosensitizers is urgently desirable for addressing the resistance of cancer cells to ionizing radiation, which is the main reason for the failure of radiotherapy. Here, it is reported for the first time that supramolecular nanomaterials can serve as an excellent nanoplatform for developing superior radiosensitizers. A new curcumin-based supramolecular nanofiber (Cur-SNF) by virtue of a self-assembling short peptide is developed, which greatly boosts the radiosensitivity of colorectal cancers to ionizing radiation. The drug-peptide conjugate Curcumin-FFE-CS-EE is synthesized and can self-assemble into small-molecule hydrogel containing CurSNFs triggered by reductant. In vitro and in vivo radiosensitization studies reveal that as compared to free curcumin Cur-SNFs show much better performance as a radiosensitizer to sensitize colorectal cancer cells to ionizing radiation thanks to the supramolecular nanostructure. Due to the exceptionally high radiosensitization efficacy, Cur-SNFs in combination with radiation realize significant reduction in tumor volume in vivo. Besides, the molecular mechanism studies demonstrate that Cur-SNFs promote the radiosensitivity of colorectal cancer cells through inhibiting radiation-induced nuclear factor kappa B activation. Cur-SNF achieves an ultralarge sensitizer enhancement ratio at 10% cell survival value of 2.01, the highest among currently reported curcumin-based radiosensitizers.