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Immunonanoparticles − an effective tool to impair harmful proteolysis in invasive breast tumor cells
Author(s) -
Obermajer Nataša,
Kocbek Petra,
Repnik Urška,
Kužnik Alenka,
Cegnar Mateja,
Kristl Julijana,
Kos Janko
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05971.x
Subject(s) - intracellular , proteolysis , proteases , cathepsin , cathepsin b , endocytosis , protease , cathepsin s , extracellular , cathepsin d , cancer research , chemistry , biology , microbiology and biotechnology , biochemistry , cell , enzyme
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 breast and other tumors in which intracellular proteolytic activity is a part of the process of malignant progression.