Import and Export of Gold Nanoparticles: Exchange Rate in Cancer Cells and Fibroblasts

Cancer is one of the leading causes of death. Radiation therapy is an important modality used in cancer treatment being highly cost-effective. Major flaw of radiotherapy is lack of selectivity between cancerous and healthy tissues. Amelioration of radiotherapy by using high-Z nanoparticles as radiation enhancers is one of potential solutions. Gold nanoparticles (AuNPs) are commonly used as radioenhancers. Understanding the interaction between cancer cells and AuNPs is essential in order to achieve best possible radioenhancing effects, while sparing healthy tissues. This work aims to elucidate interactions of ultrasmall (core size: 2.4 nm and hydrodynamic diameter (Dh): 4.5 nm) fluorescently labeled AuNPs with various human cell lines. In this perspective we measured uptake dynamics, characterized route of internalization and time of intracellular retention in various cancer cell lines and fibroblasts. Our results show that uptake dynamics and internalization pathways are strongly cell line-dependant. We also demonstrate that higher proportion of internalized nanoparticles resides in cancer cells, compared to fibroblasts, in in vitro conditions. This work highlights great complexity of cancerous cells and underlines the necessity for excellent knowledge of biological behaviour for each type of cancer. It also emphasizes the major effort needed for efficient cancer treatments and makes an appeal for further development of highly selective nanoparticles in order to hasten their utilization in clinical conditions.

Toward improving the therapeutic ratio in stereotactic radiosurgery: selective modulation of the radiation responses of both normal tissues and tumor

✓A review of the radiobiological factors that influence the response of the brain to radiation is provided in relation to stereotactic radiosurgery (SRS). The prospects for intervention after radiation treatment to selectively modulate the expression of late central nervous system (CNS) injury is considered, as well as an account of recent interest in the use of radiation enhancers to selectively increase the response of tumors to radiation. Brain necrosis in humans, after conventional irradiation, indicates that the risk of necrosis increases rapidly after an equivalent single dose of 12 or 13 Gy. When single-dose treatments are extended due to 60Co decay or planned extension of treatment times, account should be taken of the effects of the repair of sublethal radiation damage to DNA on the efficacy of treatment. Both repair capacity and repair kinetics will also influence tumor control, but parameters to quantify this effect have not yet been established. The volume of CNS tissue that has been irradiated affects the tissue response, but this effect is only significant for volumes less than 0.05 cm3. The gain obtained from irradiation of small volumes is reduced, however, when focal irradiation is given within a wider field of irradiation. Based on a vascular hypothesis explaining the pathogenesis of late CNS damage, approaches designed to selectively modulate the frequency of late CNS damage have been validated. Given the high intrinsic radioresistance of some tumors, as opposed to the presence of hypoxia, an interest has developed in the use of selective radiation enhancers in the treatment of tumors. The compound presently available has proved to be disappointing clinically due to toxicity at effective doses, when repeated administration is required. However, when given at high single doses it is less toxic and may be more effective. Less toxic radiation enhancers need to be developed.

Pharmaceutical development and medical applications of porphyrin-type macrocycles

The current state of pharmaceutical development of porphyrin-type macrocycles in medicine is highlighted. Currently, several porphyrinoid-based drugs are under various stages of development as phototherapeutic agents, X-ray radiation enhancers and boron neutron capture agents. These compounds represent a burgeoning class of pharmacological agents that are potentially useful in an array of treatment areas.