**Acknowledgements**

superficial tumors, owing to the requirement for that low‐energy (<100 keV) X‐rays be used to optimize LEE production and hence radiosensitization by the photoelectric effect. To treat deep tumors, a radioactive source may have to be encapsulated inside a gold nanoparticle (i.e., in a gold nanocage) [219]. Furthermore, if DNA specificity cannot be achieved in patients, suc‐ cessful treatment may still be possible by intratumor injection of GNPs, as recently shown by

The experimental and theoretical results of LEE impact on single‐ and double‐stranded DNA, its basic constituents, protein subunits, as well as radiosensitizers and chemotherapeutic agents alone or bound to DNA were reviewed. Experimental details of LEE interactions with these biomolecules were obtained in both the condensed and gas phases. The condensed‐phase experiments were conducted in UHV and at atmospheric pressure under environments closer to those of the cell. From these studies, which provide a fundamental comprehension of the role of TMAs in irradiated biological systems, we can arrive with considerable certainty at the following conclusions on LEE‐induced damage to biomolecules. In the low‐energy range (i.e., below the threshold for dipolar dissociation (~15 eV)), bond rupture in biomolecules occurs essentially via the formation of TMAs that decay either via autoionization with the accompa‐ nied production of dissociative electronically excited states, or into the DEA channel. The induced damage depends on a large number of factors, including electron energy, the environment and topology of the molecule, and the electrostatic or chemical binding of small radiosensitizing molecules. Such factors inevitably modify the lifetime and decay channels of

Since secondary electrons of low energy possess a large portion of the energy deposited by high‐energy radiation, any modification of how their energy deposits at crucial cellular sites is expected to have a strong radioprotective or radiosensitizing action. With DNA being the main target in radiotherapy, parameters that affect LEE‐induced DNA damage are necessarily of relevance to radiosensitivity, and the mechanisms involved must be well understood to

Many of these mechanisms are now well established as seen from the experiments and theoretical treatments reviewed in this chapter. Moreover, it has been shown that applying fundamental principles of action of LEEs to radiosensitizers or chemotherapeutic agents can lead to new strategies on how to improve radiotherapy outcomes. In particular, the role of LEEs in radiation damage was related to enhancement of the destruction of cancer cells by Pt‐ drugs and gold nanoparticles. LEEs were found to play an important role in providing guidelines in chemoradiation cancer treatment, as well as in the development of more efficient clinical protocols. Such applications point out the need for multidisciplinary studies in this field, where LEE–biomolecule interactions have become an area of intensive investigation that

transient anions, which often increase the damage cross sections.

control and modulate the biological effects of ionizing radiation.

encompasses many aspects of cancer therapy.

Shi et al. [220] and Bobyk et al. [204].

210 Radiation Effects in Materials

**9. Summary and Conclusions**

The authors gratefully express thanks for helpful comments of Dr. Andrew D. Bass and Dr. Darel J. Hunting. LS acknowledges the financial support from Canadian Institute of Health Research (CIHR, via MOP 81356 and 86676) and from Natural Sciences and Engineering Research Council of Canada (NSERC). S.P. acknowledges the financial support from the U.S. Department of Energy Office of Science, Office of Basic Energy Sciences under award number DE‐FC02‐04ER15533.
