IRGD-TRP-PK1-modified Red Blood Cell Membrane Vesicles As a New Chemotherapeutic Drug Delivery and Targeting System in Head and Neck Cancer

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. 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 and . 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. 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.