Folic Acid-Conjugated Radioluminescent Calcium Tungstate Nanoparticles as Radio-Sensitizers for Cancer Radiotherapy

Abstract

Radiation therapy is a primary treatment modality for many forms of cancer. Normally, the highest tolerable dose of ionizing radiation is used to treat tumors, but limitations imposed by normal tissue complications present challenges for local tumor control. In light of this, a class of compounds called radio-sensitizers have been developed to enhance the effectiveness of radiation. Many of these are small molecule drugs found to interact favorably with radiation therapy, but recent advances have been made using nanoparticles as radio-sensitizers. Herein, we report the utilization of radio-luminescent calcium tungstate nanoparticles that emit photoelectrons, UV-A, and visible light during X-ray irradiation, acting as effective radio-sensitizers (“Radio Luminescence Therapy”). In addition, a folic acid-functionalized form of these nanoparticles was shown to enhance radio-sensitization in vitro and in murine models of head and neck cancer. Folic acid-functionalized particles were found to decrease UV-A-induced clonogenic cell survival relative to nonfunctionalized particles. Several possible mechanisms were explored, and the folic acid-functionalized particles were found to mediate this increase in efficacy likely by activating pro-proliferative signaling through folate’s innate mitogenic activity, leading to decreased repair of UV-A-induced DNA lesions. Finally, a clinical case study of a canine sarcoma patient demonstrated the initial safety and feasibility of translating these folic acid-functionalized particles into the clinic as radio-sensitizers in the treatment of spontaneous tumors.

A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy

“…It exhibited sensitizer enhancement ratios (SER) of 1.45 and 1.21 at a 10% survival fraction. Colongenic cell survival assay showed that CaWO 4 exhibited a sensitization ratio (SER) of 1.21 at a 10% survival rate [ 52 ]. In 2017, Zhao et al studied the radiosensitization effect of GdW10 on BEL-7402 cells, and the results showed that the SER was 1.28 [ 26 ].…”

Bilirubin-Coated Radioluminescent Particles for Radiation-Induced Photodynamic Therapy

“…This mixture was then vortexed for 30 s to complete the resuspension. These particles were then filtered with a 450 nm PTFE syringe filter …”

Investigating the reactive oxygen species production of Rose Bengal and Merocyanine 540-loaded radioluminescent nanoparticles

“…[1][2][3][4] The most promising RLNP compositions utilize lanthanide ions as activators doped into various inorganic hosts such as oxides, tungstates, aluminates, oxysuldes and uorides, among others. [5][6][7][8] Lanthanide-doped nanoparticles based on a uoride host have attracted considerable attention due to their unique properties, such as wide band gap, low phonon energy, and high chemical and radiation stability. 9,10 Thus, uoride-based lanthanide-doped nanoparticles have emerged as strong candidates for achieving efficient 4f n -4f n emissions under ionizing excitation.…”