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Radiosensitization of ultrasmall GNP–PEG–cRGDfK in ALTS1C1 exposed to therapeutic protons and kilovoltage and megavoltage photons

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Version 2 2018-01-08, 16:52
Version 1 2017-11-27, 20:17
journal contribution
posted on 2018-01-08, 16:52 authored by Milad Enferadi, Sheng-Yung Fu, Ji-Hong Hong, Chuan-Jong Tung, Tsi-Chian Chao, Shiaw-Pyng Wey, Chun-Hui Chiu, Chun-Chieh Wang, Mahdi Sadeghi

Purpose: One of the promising radiosensitizers is the ultrasmall gold nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and conjugated with cyclic RGDfK (2.6 nm hydrodynamic diameter) for targeting of alpha(v) beta(3) integrin (αvβ3) in the murine ALTS1C1 glioma cell line.

Materials and methods: We investigated the uptake, toxicity and radiosensitivity of GNP–PEG–cRGDfKs in ALTS1C1 cells exposed to protons, kilovoltage photons and megavoltage photons. The in vitro uptake and toxicity of GNPs in the hepatocytes and Kupffer cells were assessed for murine AML12 hepatocyte and RAW 264.7 macrophage cell lines. The in vivo biodistribution of GNPs in the ALTS1C1 tumor model was tested using the inductively coupled plasma mass spectrometry.

Results: Results indicated GNPs accumulated in the cytoplasm with negligible toxicity for a moderate concentration of GNPs. Observed sensitizer enhancement ratios and dose enhancement factors are 1.21–1.66 and 1.14–1.33, respectively, for all radiations.

Conclusion: Ultrasmall GNP–PEG–cRGD can be considered as a radiosensitizer. For radiotherapy applications, the delivery method should be developed to increase the GNP uptake in the tumor and decrease the uptakes in undesirable organs.

Funding

The project was supported by Ministry of Science and Technology, Taiwan and Chang Gung Memorial Hospital, LinKou, Taiwan [CMRPG3E1301&2, CIRPG3D0141 and CIRPD1E0053].

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