Mechanisms of injury to normal tissue after radiotherapy: a review.

BACKGROUND: The benefits of radiotherapy for cancer have been well documented for many years, but many patients treated with radiation develop adverse effects. This study analyzed the current research into the biological basis of radiotherapy-induced normal tissue damage. METHODS: Using the PubMed and EMBASE databases, articles on adverse effects of radiotherapy on normal tissue published from January of 2005 through May of 2012 were identified. Their abstracts were reviewed for information relevant to radiotherapy-induced DNA damage and DNA repair. Articles in the reference lists that seemed relevant were reviewed with no limitations on publication date. RESULTS: Of 1751 publications, 1729 were eliminated because they did not address fundamental biology or were duplicates. The 22 included articles revealed that many adverse effects are driven by chronic oxidative stress affecting the nuclear function of DNA repair mechanisms. Among normal cells undergoing replication, cells in S phase are most radioresistant because of overexpression of DNA repair enzymes, while cells in M phase are especially radiosensitive. Cancer cells exhibit increased radiosensitivity, leading to accumulation of irreparable DNA lesions and cell death. Irradiated cells have an indirect effect on the cell cycle and survival of cocultured nonirradiated cells. Method of irradiation and linear energy transfer to cancer cells versus bystander cells are shown to have an effect on cell survival. CONCLUSIONS: Radiotherapy-induced increases in reactive oxygen species in irradiated cells may signal healthy cells by increasing metabolic stress and creating DNA lesions. The side effects of radiotherapy and bystander cell signaling may have a larger impact than previously acknowledged.

Nanoparticle systems as tools to improve drug delivery and therapeutic efficacy.

Nanoparticle-based drug delivery systems are appealing because, among other properties, they are easily manufactured and have the capacity to encapsulate a wide variety of drugs, many of which are not directly miscible with water. This review classifies nanoparticles into three broad categories based upon material composition: bio-inspired systems, synthetic systems, and inorganic systems. Each has distinct properties suitable for drug delivery applications, including their structure, composition, and pharmacokinetics (including clearance and uptake mechanisms), making each uniquely suitable for certain types of drugs. Furthermore, nanoparticles can be customized, making them ideal for a variety of applications. Advantages and disadvantages of the different systems are discussed. Strategies for improving nanoparticle efficacy include adding targeting agents on the nanoparticle surface, altering the degradation profile to control drug release, or PEGylating the surface to increase circulation times and reduce immediate clearance by the kidneys. The future of nanoparticle systems seems to be focused on further improving overall patient outcome by increasing delivery accuracy to the target area.