No abstract

Chemotherapy is commonly used in the treatment of cancers. However, the mechanism of action of many of these agents is not well understood. We present the synthesis of a two-photon f luorophore (C625) and its biological application when chemically linked to a chemotherapeutic agent (AN-152). By using two-photon laser-scanning microscopy, the drug:f luorophore conjugate can be observed directly as it interacts with receptor-positive cell lines. The results of this project visually show the receptor-mediated entry of AN-152 into the cell cytoplasm and subsequently into the nucleus. These observations will allow for better understanding of the drug's therapeutic mechanism, which is a subject of ongoing research aimed at improving present methods for cancer therapy.Two-photon processes have been drawing a great deal of attention in the last decade because of their wide range of applications. Pioneering works by Rentzepis and coworkers (1-3) have established the utility of two-photon processes in three-dimensional data storage and microfabrication. Twophoton laser-scanning microscopy (4 -7), introduced by Webb's group, has already been shown to be a powerful technique for probing the three-dimensional structure of a cell and to have inherent optical-sectioning capability without any significant interference from autofluorescence. Our recent efforts on design and synthesis of two-photon chromophores have produced highly efficient two-photon up-converters (which emit photons of a frequency higher than that of the absorbed photons); some of them even exhibit up-conversion lasing (8-10). In this paper, we report the synthesis of a two-photon fluorophore, which was coupled to a chemotherapeutic agent and used in optical tracking of its interaction and entrance in to the target cells by two-photon laser-scanning microscopy.Chemotherapy has been used widely in the treatment of cancers. However, the cellular mechanism of these agents is often not well understood. For example, whether certain chemotherapeutic drugs attach to the membrane of a cancer cell, enter the cell, or enter the nucleus affecting the DNA replication process is not well understood. Such an understanding at the cellular and molecular level will be a major advancement in biology and will lead to ways of enhancing the efficacy of chemotherapy.Chemotherapeutic agent AN-152 was made by coupling the cytotoxic agent doxorubicin (Dox) to the luteinizing hormone-releasing hormone (LH-RH) analog, ]LH-RH (11). Its design is based on the fact that specific high-affinity membrane receptors for LH-RH have been found to be expressed in many sex-linked tissue-derived cancers (12) and expressed de novo in many other cancers (13-16). In the last decade, Schally and coworkers (17-20) have developed and tested several cytotoxic LH-RH conjugates in which a wide variety of cytotoxic agents were linked to LH-RH analogs. As one of the most widely used anticancer drugs, Dox has shown to have a broad spectrum of antitumor effects (21). Its complex cytotoxic mechanism has ...

No abstract

No abstract

No abstract