| Cancer is one of the leading causes of death, and has grown as a major health care problem worldwide. Radiotherapy, together with surgery and chemotherapy, is the most effective treatment for cancer. There are plenty of examples of the curative role of radiotherapy. However, when radiotherapy is given with curative intent there is the risk of serious damage to normal tissue. Due to the radiation tolerance of the normal tissues, sometimes it is difficult to increase the radiation dose to the tumor, leading to lower local tumor control. Great effort has been made to develop new radiotherapy methods to deliver higher radiation dose with a concomitant relative sparing of normal tissues. Among these methods are Intensity Modulated Radiotherapy(IMRT), Stereotactic Radiotherapy Three-Dimensional Conformal Radiation Therapy, Fast Neutron Therapy, Proton Therapy and Boron Neutron Capture Therapy(BNCT).BNCT is a binary treatment modality that allows delivery of high-LET radiation to tumor cells while sparing surrounding normal tissues. The principle is to deliver non-radioactive nuclides, 10B, into the tumor that will react with a beam of low-energy neutrons to produce two high-energy fission particles, 7Li and 4He. The helium particle has a range of 9 urn and the lithium particle 5 urn in tissue. Since a mammalian cell diameter is about 10 urn, the particle may deposit most of its lethal energy in a single cell that has bound orinternalized 10B. Further more, a single session of BNCT is much more convenient for the patient when compared with 6-week conventional radiotherapy.Successful application of BNCT depends upon effective drug-targeting methodology for the selective delivery of boron to cancer cells.Monoclonal antibody(mAb) targeting therapy is an important modility of tumor biotherapy. After decades of intensive research, some mAb drugs have been approved by FDA.It is well known that, HER-2 is overexpressed in several types of cancer, including breast cancer, lung cancer, gastric cancer, bladder carcinoma, and its expression is similar in primary tumors and corresponding metastases. On the contrary, its expression in normal tissues is at a low level. Thus, HER-2 is of interest as a potential target. Trastuzumab (Herceptin), a recombinant humanized anti-HER-2 mAb, is the first clinically available oncogene-targeted therapeutic agent for treatment of solid tumor.Liposomes have gained considerable interest as drug deliver tool for the therapy of cancer. They have many therapeutic advantages, good biocompatible, large drug carrying capacity, colloidal size, controllable surface and membrane properties. Water Soluble boronated Acridine (WSA), a candidate drug for BNCT, consists of a boron cage with 10 boron atoms coupled to an acridine analogue and a spermidine to increase water solubility. It has been designed and developed by our collaborators as a candidate drug for BNCT with a purpose to reach into the nucleus of the tumor cells . Due to its charge, WSA can be actively loaded into liposomes using a pH-gradient procedure. 105 to 106 boron atoms can be loaded in each liposome, which is enough to make the liposomes interesting for therapy.Immunoliposomes have become feasible as a result of parallel advances in the areas of liposome research and mAb technology, which in principle now can be combined for tumor-targeted drug delivery. The utilization ofimmunoliposomes as boron carriers for BNCT offers several attractive features. Since tumor targeting agents could be linked to liposomes, the incorporated boron compound is not required to have its own tumor-seeking capability. It will be of interest to prepare WSA loaded liposomes linked with Trastuzumab, since both Trastuzumab (Herceptin) and liposomes (Stealth) have been approved by FDA.The goal of the study:1. Development of HER-2-targeted WSA-containing liposomes as potential drug delivery vehicle for BNCT, including optimization of the developing conditions and study on the stability of the conjugates.2. Investiga...
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