PEG-PLA-Coated and Uncoated Radio-Luminescent CaWO4 Micro- and Nanoparticles for Concomitant Radiation and UV-A/Radio-Enhancement Cancer Treatments

Sung Duk Jo; Jaewon Lee; Min Kyung Joo; Vincenzo J. Pizzuti; Nicholas J. Sherck; Slgi Choi; Beom Suk Lee; Sung Ho Yeom; Sang Yoon Kim; Sun Hwa Kim; Ick Chan Kwon; You Yeon Won

doi:10.1021/acsbiomaterials.8b00119

PEG-PLA-Coated and Uncoated Radio-Luminescent CaWO₄ Micro- and Nanoparticles for Concomitant Radiation and UV-A/Radio-Enhancement Cancer Treatments

Sung Duk Jo, Jaewon Lee, Min Kyung Joo, Vincenzo J. Pizzuti, Nicholas J. Sherck, Slgi Choi, Beom Suk Lee, Sung Ho Yeom, Sang Yoon Kim, Sun Hwa Kim, Ick Chan Kwon, You Yeon Won

KU-KIST Graduate School of Converging Science and Technology

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

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 γ ray or X-ray photons. In vitro tests demonstrate that unoptimized RLP materials (uncoated CaWO₄ (CWO) microparticles (MPs) and PEG-PLA-coated CWO nanoparticles (NPs)) induce a significant enhancement of the tumor-suppressive effect of X-rays and γ 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.

Original language	English
Pages (from-to)	1445-1462
Number of pages	18
Journal	ACS Biomaterials Science and Engineering
Volume	4
Issue number	4
DOIs	https://doi.org/10.1021/acsbiomaterials.8b00119
Publication status	Published - 2018 Apr 9

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acsbiomaterials.8b00119

Cite this

Jo, S. D., Lee, J., Joo, M. K., Pizzuti, V. J., Sherck, N. J., Choi, S., Lee, B. S., Yeom, S. H., Kim, S. Y., Kim, S. H., Kwon, I. C., & Won, Y. Y. (2018). PEG-PLA-Coated and Uncoated Radio-Luminescent CaWO₄ Micro- and Nanoparticles for Concomitant Radiation and UV-A/Radio-Enhancement Cancer Treatments. ACS Biomaterials Science and Engineering, 4(4), 1445-1462. https://doi.org/10.1021/acsbiomaterials.8b00119

Jo, SD, Lee, J, Joo, MK, Pizzuti, VJ, Sherck, NJ, Choi, S, Lee, BS, Yeom, SH, Kim, SY, Kim, SH, Kwon, IC & Won, YY 2018, 'PEG-PLA-Coated and Uncoated Radio-Luminescent CaWO₄ Micro- and Nanoparticles for Concomitant Radiation and UV-A/Radio-Enhancement Cancer Treatments', ACS Biomaterials Science and Engineering, vol. 4, no. 4, pp. 1445-1462. https://doi.org/10.1021/acsbiomaterials.8b00119

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title = "PEG-PLA-Coated and Uncoated Radio-Luminescent CaWO4 Micro- and Nanoparticles for Concomitant Radiation and UV-A/Radio-Enhancement Cancer Treatments",

abstract = "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 γ ray or X-ray photons. In vitro tests demonstrate that unoptimized RLP materials (uncoated CaWO4 (CWO) microparticles (MPs) and PEG-PLA-coated CWO nanoparticles (NPs)) induce a significant enhancement of the tumor-suppressive effect of X-rays and γ 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.",

author = "Jo, {Sung Duk} and Jaewon Lee and Joo, {Min Kyung} and Pizzuti, {Vincenzo J.} and Sherck, {Nicholas J.} and Slgi Choi and Lee, {Beom Suk} and Yeom, {Sung Ho} and Kim, {Sang Yoon} and Kim, {Sun Hwa} and Kwon, {Ick Chan} and Won, {You Yeon}",

note = "Funding Information: Funding for this research was provided by the Purdue Office of the Executive Vice President for Research and Partnerships (OEVPRP, New NIH R01 Program), the Indiana Clinical and Translational Sciences Institute (CTSI, the Collaboration in Translational Research (CTR) Pilot Grant Program), the Purdue University Center for Cancer Research (PCCR, NIH Grant P30 CA023168; SIRG Graduate Research Assistantship, Shared Resource Biological Evaluation Project, and Phase I Concept Award), LoDos Theranostics LLC (Gift Grant), the School of Chemical Engineering at Purdue University, the U.S. National Science Foundation (NSF, CBET-1264336), the Global Innovative Research Center (GiRC) Program of the National Research Foundation of Korea (2012k1A1A2A01056095), and the “Global RNAi Carrier Initiative” Intramural Research Program of the Korea Institute of Science and Technology (KIST). We would like to thank Dr. Marc Mendonca in the Department of Radiation Oncology at the Indiana University School of Medicine for allowing us to use his 160 kV X-ray irradiator in order to obtain the 160 kV dosimetry data shown in Figure 4,,. The HN31 cell line was generously provided by Dr. Jeffrey N. Myers at the MD Anderson Cancer Center. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

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doi = "10.1021/acsbiomaterials.8b00119",

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T1 - PEG-PLA-Coated and Uncoated Radio-Luminescent CaWO4 Micro- and Nanoparticles for Concomitant Radiation and UV-A/Radio-Enhancement Cancer Treatments

AU - Jo, Sung Duk

AU - Lee, Jaewon

AU - Joo, Min Kyung

AU - Pizzuti, Vincenzo J.

AU - Sherck, Nicholas J.

AU - Choi, Slgi

AU - Lee, Beom Suk

AU - Yeom, Sung Ho

AU - Kim, Sang Yoon

AU - Kim, Sun Hwa

AU - Kwon, Ick Chan

AU - Won, You Yeon

N1 - Funding Information: Funding for this research was provided by the Purdue Office of the Executive Vice President for Research and Partnerships (OEVPRP, New NIH R01 Program), the Indiana Clinical and Translational Sciences Institute (CTSI, the Collaboration in Translational Research (CTR) Pilot Grant Program), the Purdue University Center for Cancer Research (PCCR, NIH Grant P30 CA023168; SIRG Graduate Research Assistantship, Shared Resource Biological Evaluation Project, and Phase I Concept Award), LoDos Theranostics LLC (Gift Grant), the School of Chemical Engineering at Purdue University, the U.S. National Science Foundation (NSF, CBET-1264336), the Global Innovative Research Center (GiRC) Program of the National Research Foundation of Korea (2012k1A1A2A01056095), and the “Global RNAi Carrier Initiative” Intramural Research Program of the Korea Institute of Science and Technology (KIST). We would like to thank Dr. Marc Mendonca in the Department of Radiation Oncology at the Indiana University School of Medicine for allowing us to use his 160 kV X-ray irradiator in order to obtain the 160 kV dosimetry data shown in Figure 4,,. The HN31 cell line was generously provided by Dr. Jeffrey N. Myers at the MD Anderson Cancer Center. Publisher Copyright: © 2018 American Chemical Society.

PY - 2018/4/9

Y1 - 2018/4/9

N2 - 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 γ ray or X-ray photons. In vitro tests demonstrate that unoptimized RLP materials (uncoated CaWO4 (CWO) microparticles (MPs) and PEG-PLA-coated CWO nanoparticles (NPs)) induce a significant enhancement of the tumor-suppressive effect of X-rays and γ 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.

AB - 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 γ ray or X-ray photons. In vitro tests demonstrate that unoptimized RLP materials (uncoated CaWO4 (CWO) microparticles (MPs) and PEG-PLA-coated CWO nanoparticles (NPs)) induce a significant enhancement of the tumor-suppressive effect of X-rays and γ 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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