Pancreatic cancer is among the leading causes of cancer-related death and remains a formidable therapeutic challenge. To date, surgical resection and chemotherapy have been the standards of care. Methotrexate (MTX), which is recognized as a refractory drug for pancreatic cells, was conjugated to the surface of LiYF:Ce nanoparticles (NP-MTX) through a photocleavable linker molecule. When LiYF:Ce NPs are stimulated by X-rays, they emit light, which induces the photocleavage of the photolabile linker molecule to release MTX. MTX can target pancreatic tumors, which overexpress folic acid (FA) receptors and are internalized into the cell through receptor-mediated endocytosis. The synergistic effect of the NP-MTX treatment initiated by X-ray irradiation occurs due to the combination of nanoparticle sensitization and the radiosensitizing chemotherapy of the photocleaved MTX molecule. This dual sensitization effect mediated by NP-MTX enabled 40% dose enhancement, which corresponded with an increase in the generation of cytotoxic cellular reactive oxygen species (ROS) and enhanced S phase arrest within the cell cycle. The delivery of an ultralow radiation dose of 0.1 Gy resulted in the photocleavage of MTX from NP-MTX, and this strategy demonstrated efficacy against AsPC-1 and PANC-1 xenografted pancreatic tumors.
About The Expert
Divinah Manoharan
Li-Chan Chang
Liu-Chun Wang
Yan-Shen Shan
Forn-Chia Lin
Lai-Chin Wu
Hwo-Shuenn Sheu
Wen-Pin Su
Chen-Sheng Yeh
References
PubMed