Dual Potential of Cetuximab Conjugated Hydroxyapatite Zirconium Nanoparticle as Nanocarrier for Radioenhancer in X-Ray Dynamic Therapy and 177Lu-based Radioimmunotherapy of Lung Cancer

Nanotheranostics. 2025 Mar 3;9(1):82-94. doi: 10.7150/ntno.101699. eCollection 2025.

Abstract

This study aimed to synthesize cetuximab (CTX) conjugated hydroxyapatite zirconium (HApZr-CTX) as a nanocarrier for active delivery of photosensitizer and therapeutic radionuclide. The system enabled targeted radioenhancer in X-ray dynamic therapy and radioimmunotherapy for lung cancer. The results showed that HApZr-CTX had the main characteristics of hydroxyapatite crystal in X-ray powder diffraction (XRD), with particle size twice bigger, according to DLS-PSA and TEM measurements. Cellular ROS generation was elevated almost three times in A549 cells after being treated using 125 µg/mL HApZr-CTX and irradiated with 5 Gy of X-ray photon compared to untreated cells. The viability of the treated lung cancer cell line decreased after exposure to external radiation. Moreover, as a radioimmunotherapy candidate, 177Lu was successfully loaded into HApZr-CTX nanocarrier and internalized in A549 more than half of the given dose after 0.5 h incubation. [177Lu]Lu-HApZr-CTX was primarily accumulated in the lung organs of healthy mice one-hour post-injection. In conclusion, HApZr-CTX nanoparticles have the potential to be used as a radioenhancer in X-ray dynamic therapy and radioimmunotherapy for lung cancer therapy.

Keywords: Cetuximab; Hydroxyapatite; Lung cancer; Nanoparticle; Radioimmunotherapy; X-ray dynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Cetuximab* / chemistry
  • Cetuximab* / pharmacology
  • Drug Carriers / chemistry
  • Durapatite* / chemistry
  • Humans
  • Lung Neoplasms* / therapy
  • Lutetium* / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Radiation-Sensitizing Agents / administration & dosage
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacology
  • Radioimmunotherapy* / methods
  • Radioisotopes* / chemistry
  • Zirconium* / chemistry

Substances

  • Cetuximab
  • Zirconium
  • Lutetium
  • Durapatite
  • Radioisotopes
  • Lutetium-177
  • Radiation-Sensitizing Agents
  • Drug Carriers