iRGD-TRP-PK1-modified red blood cell membrane vesicles as a new chemotherapeutic drug delivery and targeting system in head and neck cancer

Background: Chemotherapy is essential for treating tumors, including head and neck cancer (HNC). However, the toxic side effects of chemotherapeutic drugs limit their widespread use. Therefore, a targeted delivery system that can transport the drug to the pathological site while minimizing damage to healthy tissues is urgently needed. Methods: Application of animal imaging, flow cytometry, fluorescence staining, cell activity assay, transmission electron microscopy, western blotting and immunohistochemistry to evaluate the targeting and killing effects of internalizing RGD peptide (iRGD)-transient receptor potential (TRP)-PK1-modified red blood cell vesicles (RBCVs) on HNC cells in vitro and in vivo. Results: TRP-PK1 was ligated to iRGD, enabling autonomous insertion into the lipid bilayer. Additionally, RBCVs were labeled with iRGD-TRP-PK1 to achieve tumor targeting. Based on the self-assembly capability of TRP-PK1 to form a "leakage potassium" channel on the biofilm, RBCVs were fragmented within the high-potassium (K⁺) environment inside tumor cells. This fragmentation facilitated the release of the drug loaded onto the RBCVs. Conclusion: The advantageous properties of TRP-PK1 are utilized in our design, resulting in a cost-effective and straightforward approach to drug delivery and release. Ultimately, the objective of suppressing tumor growth while minimizing side effects was accomplished by iRGD-TRP-PK1-modified RBCVs in our study. These findings provide novel insights into the enhancement of targeted delivery systems and present promising avenues for the treatment of HNC.