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

Theranostics. 2025 Jan 1;15(1):86-102. doi: 10.7150/thno.99481. eCollection 2025.

Abstract

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.

Keywords: Drug Delivery; Head and Neck Cancer; Red Blood Cell Membrane Vesicles; Targeting System; iRGD-TRP-PK1.

MeSH terms

  • Animals
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Drug Delivery Systems* / methods
  • Erythrocyte Membrane / chemistry
  • Erythrocyte Membrane / drug effects
  • Erythrocyte Membrane / metabolism
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oligopeptides* / administration & dosage
  • Oligopeptides* / chemistry

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • arginyl-glycyl-aspartic acid