tailieunhanh - Báo cáo khoa học: Immunonanoparticles ) an effective tool to impair harmful proteolysis in invasive breast tumor cells

Breast cancer cells exhibit excessive proteolysis, which is responsible for extensive extracellular matrix degradation, invasion and metastasis. Besides other proteases, lysosomal cysteine protease cathepsin B has been impli-cated in these processes and the impairment of its intracellular activity was suggested to reduce harmful proteolysis and hence diminish progression of breast tumors. | ễFEBS Journal Immunonanoparticles - an effective tool to impair harmful proteolysis in invasive breast tumor cells Natasa Obermajer1 Petra Kocbek1 Urska Repnik2 Alenka KuZnik1 Mateja Cegnar1 Julijana Kristl1 and Janko Kos1 2 1 Faculty of Pharmacy University of Ljubljana Slovenia 2 Institute Jozef Stefan Jamova Ljubljana Slovenia Keywords antibody-coated breast cancer cystatin cytokeratin immunonanoparticles Correspondence J. Kos Department of Pharmaceutical Biology University of Ljubljana Askerceva 7 1000 Ljubljana Slovenia Fax 386 1425 80 31 Tel 386 40 792 639 E-mail Website http content view full 107 Received 25 April2007 revised 19 June 2007 accepted 2 July 2007 doi Breast cancer cells exhibit excessive proteolysis which is responsible for extensive extracellular matrix degradation invasion and metastasis. Besides other proteases lysosomal cysteine protease cathepsin B has been implicated in these processes and the impairment of its intracellular activity was suggested to reduce harmful proteolysis and hence diminish progression of breast tumors. Here we present an effective system composed of poly D L-lactide-coglycolide nanoparticles a specific anti-cytokeratin monoclonal IgG and cystatin a potent protease inhibitor that can neutralize the excessive intracellular proteolytic activity as well as invasive potential of breast tumor cells. The delivery system distinguishes between breast and other cells due to the monoclonal antibody specifically recognizing cytokeratines on the membrane of breast tumor cells. Bound nanoparticles are rapidly internalized by means of endocytosis releasing the inhibitor cargo within the lysosomes. This enables intracellular cathepsin B proteolytic activity to be inhibited reducing the invasive and metastatic potential of tumor cells without affecting proteolytic functions in normal cells and processes. This approach may be applied for treatment of .