PEG-PLA-coated and uncoated radio-luminescent CaWO4 micro/nanoparticles for concomitant radiation/UV-A and radio-enhancement cancer treatments
- PEG-PLA-coated and uncoated radio-luminescent CaWO4 micro/nanoparticles for concomitant radiation/UV-A and radio-enhancement cancer treatments
- 권익찬; 김선화; 이범석; 조성덕; 주민경; Jaewon Lee; Vincenzo J. Pizzuti; Nicholas J. Sherck; Slgi Choi; Sung Ho Yeom; Sang Yoon Kim; 원유연
- Issue Date
- ACS biomaterials science & engineering
- VOL 4, NO 4-1462
- Currently, there is great interest in the development of ways to achieve the benefits of radiation treatments with reduced negative effects. The present study demonstrates the utilization of radio-luminescent particles (RLPs) as a means to achieve radio-sensitization and enhancement and their ability to affect head-and neck-cancer-cell cultures (in vitro) and xenografts (in vivo). Our approach utilizes a naturally abundant radio-luminescent mineral, calcium tungstate (CaWO4), in its micro or nanoparticulate form for generating secondary UV-A light by gamma ray or X-ray photons. In vitro tests demonstrate that unoptimized RLP materials (uncoated CaWO4 (CWO) microparticles (MPs) and PEG PLA-coated CWO nanopartides (NPs)) induce a significant enhancement of the tumor-suppressive effect of X-rays and gamma rays in both radio-sensitive-and radio resistant-cancer models; uncoated CWO MPs and PEG PLA-coated CWO NPs demonstrate comparable radio-sensitization efficacies in vitro. Mechanistic studies reveal that concomitant CaWO4 causes increased mitotic death in radio-resistant cells treated with radiation, whereas CaWO4 sensitizes radio-sensitive cells to X-ray-induced apoptosis and necrosis. The radio sensitization efficacy of intratumorally injected CaWO4 particles (uncoated CWO MPs and PEG PLA-coated CWO NPs) is also evaluated in vivo in mouse head-and neck-cancer xenografts. Uncoated CWO MPs suppress tumor growth more effectively than PEG PLA-coated CWO NPs. On the basis of theoretical considerations, an argument is proposed that uncoated CWO MPs release subtoxic levels of tungstate ions, which cause increased photoelectric-electron-emission effects. The effect of folic acid functionalization on the in vitro radio-sensitization behavior produced by PEG PLA-coated CWO NPs is studied. Surface folic acid results in a significant improvement in the radio-sensitization efficiency of CaWO4.
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