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

TL;DR

Researchers developed a nanoparticle that can deliver radiation therapy to lung cancer cells using X-rays and a radioactive isotope, improving treatment effectiveness.

Contribution

A novel CTX-conjugated HApZr nanoparticle was created for dual use in X-ray dynamic therapy and radioimmunotherapy.

Findings

HApZr-CTX nanoparticles showed enhanced ROS generation in A549 cells under X-ray irradiation.

The nanocarrier successfully loaded 177Lu and was internalized by lung cancer cells.

In mice, [177Lu]Lu-HApZr-CTX accumulated primarily in the lungs after injection.

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.

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