Radiosensitization of ultrasmall GNP-PEG-cRGDfK in ALTS1C1 exposed to therapeutic protons and kilovoltage and megavoltage photons
圖文摘要說明
本研究開發了一種功能化的超小金奈米粒子 (GNP-PEG-cRGDfK)，作為腦膠質瘤放射治療的增敏劑。此奈米粒子的核心為 1.8 奈米的金粒子，外層包覆聚乙二醇 (PEG) 以增加其在血液中的穩定性，並接上環肽 cRGDfK。此環肽能專一性地靶向腦膠質瘤細胞表面過度表現的 αvβ3 整合素，從而將金奈米粒子精準遞送至腫瘤細胞。研究結果顯示，此奈米粒子能有效累積於腫瘤細胞質內，並在質子、千伏光子及百萬伏光子等不同放射線照射下，顯著提升對腫瘤細胞的殺傷效果，具有作為高效放射增敏劑的潛力。
Abstract
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.
Keywords: ALTS1C1; GNP; cyclic RGD; proton therapy; radiosensitization.
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