Abstract
Gold nanoparticles (AuNPs) could serve as potential radiotherapy sensitizers because of their exceptional biocompatibility and high-Z material nature; however, since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries, whether surface ligands can affect their radiosensitization has seldom been investigated in the radiosensitization of AuNPs. By conducting head-to-head comparison on radiosensitization of two kinds of ultrasmall (~2 nm) near-infrared (NIR) emitting AuNPs that are coated with zwitterionic glutathione and neutral polyethylene glycol (PEG) ligands, respectively, we found that zwitterionic glutathione coated AuNPs (GS-AuNPs) can reduce survival rates of MCF-7 cells under irradiation of clinically used megavoltage photon beam at low dosage of ~2.25 Gy. On the other hand, PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation, clearly indicating the key role of surface chemistry in radiosensitization of AuNPs. More detailed studies suggested that such difference was independent of cellular uptake and its efficiency, but might be related to the ligand-induced difference in photoelectron generation and/or interactions between AuNPs and X-ray triggered reactive oxygen species (ROS).
Highlights
Radiation therapy, using high-energy ionizing radiation to damage the DNA of cancerous cells, has been a major cancer treatment in the clinical practices.[1,2] ionizing radiation itself cannot di®erentiate malignant tissues from healthy ones
While the cell uptake study showed that the GSAuNPs can be much more e±ciently internalized by MCF-7 cells than that of the PEG-AuNPs ($ 20 fold di®erence after 24 h incubation), our further studies showed that the distinct radiosensitization behaviors of GS-AuNPs and PEG-AuNPs are independent of their cellular uptake e±ciency but originated from distinct radiosensitization enhancements governed by surface ligands
The GS-AuNPs have a core size of 2:26 Æ 0:25 nm and Hydrodynamic diameters (HDs) of 4:08 Æ 0:95 nm in PBS; the PEG-AuNPs have a core size of 1:82 Æ 0:34 nm and HD of 5:83 Æ 1:31 nm in PBS
Summary
Radiation therapy, using high-energy ionizing radiation to damage the DNA of cancerous cells, has been a major cancer treatment in the clinical practices.[1,2] ionizing radiation itself cannot di®erentiate malignant tissues from healthy ones. Gold nanoparticles (AuNPs) have been extensively studied for radiosensitizer applications.[9] Zhang et al investigated the radiosensitization e®ect of di®erent-sized (4.8–46.6 nm) PEG-coated AuNPs in vitro and in vivo under 662 KeV photon radiation and found that AuNPs with core sizes of 12.1 nm and 27.3 nm showed high radiation enhancement.[10] Burn et al compared the radiation enhancement factors of di®erent-sized (8–92 nm) AuNPs in DNA solutions and revealed that large AuNPs had greater radiation enhancement under 50 KeV photon radiation.[11] While these studies have implied that the particle size of AuNPs played a key role in radiosensitization, another key structural factor, surface chemistry that has signicant a®ect on the interactions between NPs and biological systems,[12,13] was often ignored in these studies. While the cell uptake study showed that the GSAuNPs can be much more e±ciently internalized by MCF-7 cells than that of the PEG-AuNPs ($ 20 fold di®erence after 24 h incubation), our further studies showed that the distinct radiosensitization behaviors of GS-AuNPs and PEG-AuNPs are independent of their cellular uptake e±ciency but originated from distinct radiosensitization enhancements governed by surface ligands
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