Article
Development of PBCA NPs as Carrier System for the Treatment of Brain Tumors and for the Gene Therapy
Search Medline for
Authors
Published: | March 20, 2006 |
---|
Outline
Text
According to estimation of the Federal Medical Society, about 10 per cent of all cancer illnesses my be attributed to a hereditary tumor arrangement. Worldwide, brain tumor is considered the most common among adults. 180,000 new cases of different brain tumors arise annually in the USA, which result into a very high mortality rate. Reasons for this high number of deaths are penetration lacking of the blood-brain barrier. The principal purpose of our studies is the development of PBCA NPs both for the treatment of tumors (particularly brain tumors), and for use as transport system for gene therapy. Our laboratory cooperates very closely with the enterprise NanoDel Technologies GmbH in Magdeburg, which develops nanoparticles on PBCA basis as carrier system for active substances and DNA. The PBCA NPs are biologically degradable and make transport through the blood-brain barrier possible. We have already found in our previous studies that treatment of animals with the Doxorubicin PBCA Nanoparticle complex leads to an extended life span of a treated animal compared to a control animal. Aside from binding medicines and active substances, the loading of nanoparticle with DNA, DNA Oligos, and/or siRNA, is likewise possible. After binding of FITC AON to PBCA followed by coating with Tween® 80, i. v. Injection leads to a concentration increase in the brain of FITC AON NP injected animals in the compared to FITC AON (FITC AON) alone. The gene therapy provides a new way to fight genetic diseases.One can divide the gene transfer in cells into two main groups, i.e. viral and non viral vectors.It is important to develop non-viral methods since viral vectors are proving to be inefficient. However viral vector have additional advantages, like their ability, to transport very large genes such as CFTR gene (120 KB). The nanoparticles we use make it possible to overcome the blood-brain barrier (BHS). Genes bound to PBCA NPs could became expressed in the ZNS after being delivered centrally via i. v. injection. Preliminary studies had shown that the DNA binding to PBCA NPs is possible. The expression of GFP in 293T-Zellen was found to be detectable, but would have to be further optimised.